NM_020975.6(RET):c.443_445del (p.Ser148del) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: May 1, 2024
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV004780639.1

Allele description [Variation Report for NM_020975.6(RET):c.443_445del (p.Ser148del)]

NM_020975.6(RET):c.443_445del (p.Ser148del)

Gene:

RET:ret proto-oncogene [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

10q11.21

Genomic location:

Preferred name:

NM_020975.6(RET):c.443_445del (p.Ser148del)

HGVS:

NC_000010.11:g.43102447_43102449del
NG_007489.1:g.30379_30381del
NM_000323.2:c.443_445delCCT
NM_001406743.1:c.443_445del
NM_001406744.1:c.443_445del
NM_001406759.1:c.443_445del
NM_001406760.1:c.443_445del
NM_001406761.1:c.338-24_338-22del
NM_001406762.1:c.338-24_338-22del
NM_001406763.1:c.443_445del
NM_001406764.1:c.338-24_338-22del
NM_001406765.1:c.443_445del
NM_001406766.1:c.337+1725_337+1727del
NM_001406767.1:c.337+1725_337+1727del
NM_001406768.1:c.338-24_338-22del
NM_001406769.1:c.443_445del
NM_001406770.1:c.337+1725_337+1727del
NM_001406771.1:c.443_445del
NM_001406772.1:c.443_445del
NM_001406773.1:c.443_445del
NM_001406774.1:c.338-24_338-22del
NM_001406775.1:c.337+1725_337+1727del
NM_001406776.1:c.337+1725_337+1727del
NM_001406777.1:c.337+1725_337+1727del
NM_001406778.1:c.337+1725_337+1727del
NM_001406779.1:c.443_445del
NM_001406780.1:c.443_445del
NM_001406781.1:c.443_445del
NM_001406782.1:c.443_445del
NM_001406783.1:c.338-24_338-22del
NM_001406784.1:c.74-6584_74-6582del
NM_001406785.1:c.443_445del
NM_001406786.1:c.338-24_338-22del
NM_001406787.1:c.443_445del
NM_001406788.1:c.337+1725_337+1727del
NM_001406789.1:c.337+1725_337+1727del
NM_001406790.1:c.337+1725_337+1727del
NM_001406791.1:c.337+1725_337+1727del
NM_001406792.1:c.74-9652_74-9650del
NM_001406793.1:c.74-9652_74-9650del
NM_001406794.1:c.74-9652_74-9650del
NM_020629.2:c.443_445delCCT
NM_020630.7:c.443_445del
NM_020975.4:c.443_445del
NM_020975.6:c.443_445delMANE SELECT
NP_000314.1:p.Ser148del
NP_001393672.1:p.Ser148del
NP_001393673.1:p.Ser148del
NP_001393688.1:p.Ser148del
NP_001393689.1:p.Ser148del
NP_001393692.1:p.Ser148del
NP_001393694.1:p.Ser148del
NP_001393698.1:p.Ser148del
NP_001393700.1:p.Ser148del
NP_001393701.1:p.Ser148del
NP_001393702.1:p.Ser148del
NP_001393708.1:p.Ser148del
NP_001393709.1:p.Ser148del
NP_001393710.1:p.Ser148del
NP_001393711.1:p.Ser148del
NP_001393714.1:p.Ser148del
NP_001393716.1:p.Ser148del
NP_065680.1:p.Ser148del
NP_065681.1:p.Ser148del
NP_065681.1:p.Ser148del
NP_066124.1:p.Ser148del
NP_066124.1:p.Ser148del
LRG_518t1:c.443_445del
LRG_518t2:c.443_445del
LRG_518:g.30379_30381del
LRG_518p1:p.Ser148del
LRG_518p2:p.Ser148del
NC_000010.10:g.43597893_43597895del
NC_000010.10:g.43597895_43597897del
NM_020630.4:c.443_445delCCT
NM_020975.4:c.443_445delCCT

Protein change:

S148del

Molecular consequence:

NM_001406743.1:c.443_445del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406744.1:c.443_445del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406759.1:c.443_445del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406760.1:c.443_445del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406763.1:c.443_445del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406765.1:c.443_445del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406769.1:c.443_445del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406771.1:c.443_445del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406772.1:c.443_445del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406773.1:c.443_445del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406779.1:c.443_445del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406780.1:c.443_445del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406781.1:c.443_445del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406782.1:c.443_445del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406785.1:c.443_445del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406787.1:c.443_445del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_020630.7:c.443_445del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_020975.6:c.443_445del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_000323.2:c.443_445delCCT - inframe_indel - [Sequence Ontology: SO:0001820]
NM_020629.2:c.443_445delCCT - inframe_indel - [Sequence Ontology: SO:0001820]
NM_001406761.1:c.338-24_338-22del - intron variant - [Sequence Ontology: SO:0001627]
NM_001406762.1:c.338-24_338-22del - intron variant - [Sequence Ontology: SO:0001627]
NM_001406764.1:c.338-24_338-22del - intron variant - [Sequence Ontology: SO:0001627]
NM_001406766.1:c.337+1725_337+1727del - intron variant - [Sequence Ontology: SO:0001627]
NM_001406767.1:c.337+1725_337+1727del - intron variant - [Sequence Ontology: SO:0001627]
NM_001406768.1:c.338-24_338-22del - intron variant - [Sequence Ontology: SO:0001627]
NM_001406770.1:c.337+1725_337+1727del - intron variant - [Sequence Ontology: SO:0001627]
NM_001406774.1:c.338-24_338-22del - intron variant - [Sequence Ontology: SO:0001627]
NM_001406775.1:c.337+1725_337+1727del - intron variant - [Sequence Ontology: SO:0001627]
NM_001406776.1:c.337+1725_337+1727del - intron variant - [Sequence Ontology: SO:0001627]
NM_001406777.1:c.337+1725_337+1727del - intron variant - [Sequence Ontology: SO:0001627]
NM_001406778.1:c.337+1725_337+1727del - intron variant - [Sequence Ontology: SO:0001627]
NM_001406783.1:c.338-24_338-22del - intron variant - [Sequence Ontology: SO:0001627]
NM_001406784.1:c.74-6584_74-6582del - intron variant - [Sequence Ontology: SO:0001627]
NM_001406786.1:c.338-24_338-22del - intron variant - [Sequence Ontology: SO:0001627]
NM_001406788.1:c.337+1725_337+1727del - intron variant - [Sequence Ontology: SO:0001627]
NM_001406789.1:c.337+1725_337+1727del - intron variant - [Sequence Ontology: SO:0001627]
NM_001406790.1:c.337+1725_337+1727del - intron variant - [Sequence Ontology: SO:0001627]
NM_001406791.1:c.337+1725_337+1727del - intron variant - [Sequence Ontology: SO:0001627]
NM_001406792.1:c.74-9652_74-9650del - intron variant - [Sequence Ontology: SO:0001627]
NM_001406793.1:c.74-9652_74-9650del - intron variant - [Sequence Ontology: SO:0001627]
NM_001406794.1:c.74-9652_74-9650del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005389337	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (May 1, 2024)	germline	clinical testing	Citation Link,
SCV005393848	Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 8, 2023)	paternal	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005389337

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(May 1, 2024)

germline

clinical testing

Citation Link,

SCV005393848

Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 8, 2023)

paternal

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	paternal	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV005389337.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; In-frame deletion of one amino acid in a non-repeat region; This variant is associated with the following publications: (PMID: 24577265, 30693022, 37193168, 14633923)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn, SCV005393848.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	paternal	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 24, 2024

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