NM_017838.4(NHP2):c.355G>C (p.Gly119Arg) AND Dyskeratosis congenita

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 12, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001988203.4

Allele description [Variation Report for NM_017838.4(NHP2):c.355G>C (p.Gly119Arg)]

NM_017838.4(NHP2):c.355G>C (p.Gly119Arg)

Genes:

NHP2:NHP2 ribonucleoprotein [Gene - OMIM - HGNC]
RMND5B:required for meiotic nuclear division 5 homolog B [Gene - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q35.3

Genomic location:

Preferred name:

NM_017838.4(NHP2):c.355G>C (p.Gly119Arg)

HGVS:

NC_000005.10:g.178149820C>G
NG_011765.1:g.9141G>C
NM_001034833.2:c.249G>C
NM_001288794.2:c.*1788C>G
NM_001288795.2:c.*1788C>G
NM_001396110.1:c.483G>C
NM_017838.4:c.355G>CMANE SELECT
NM_022762.5:c.*1788C>GMANE SELECT
NP_001030005.1:p.Gln83His
NP_001383039.1:p.Gln161His
NP_060308.1:p.Gly119Arg
NP_060308.1:p.Gly119Arg
LRG_346t1:c.355G>C
LRG_346:g.9141G>C
LRG_346p1:p.Gly119Arg
NC_000005.9:g.177576821C>G
NM_017838.3:c.355G>C

Protein change:

G119R

Links:

dbSNP: rs750874926

NCBI 1000 Genomes Browser:

rs750874926

Molecular consequence:

NM_001288794.2:c.*1788C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001288795.2:c.*1788C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_022762.5:c.*1788C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001034833.2:c.249G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001396110.1:c.483G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_017838.4:c.355G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Dyskeratosis congenita
Identifiers:: MONDO: MONDO:0015780; MedGen: C0265965; OMIM: PS127550

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002259581	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 12, 2021)	germline	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

SCV002259581

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 12, 2021)

germline

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002259581.3

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with NHP2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 119 of the NHP2 protein (p.Gly119Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine.

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

Last Updated: Sep 29, 2024

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