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NM_000448.3(RAG1):c.2442G>T (p.Glu814Asp) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 31, 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:
RCV001041164.9

Allele description [Variation Report for NM_000448.3(RAG1):c.2442G>T (p.Glu814Asp)]

NM_000448.3(RAG1):c.2442G>T (p.Glu814Asp)

Gene:
RAG1:recombination activating 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11p12
Genomic location:
Preferred name:
NM_000448.3(RAG1):c.2442G>T (p.Glu814Asp)
Other names:
NM_000448.3(RAG1):c.2442G>T; p.Glu814Asp
HGVS:
  • NC_000011.10:g.36575746G>T
  • NG_007528.1:g.12734G>T
  • NM_000448.3:c.2442G>TMANE SELECT
  • NM_001377277.1:c.2442G>T
  • NM_001377278.1:c.2442G>T
  • NM_001377279.1:c.2442G>T
  • NM_001377280.1:c.2442G>T
  • NP_000439.1:p.Glu814Asp
  • NP_000439.2:p.Glu814Asp
  • NP_001364206.1:p.Glu814Asp
  • NP_001364207.1:p.Glu814Asp
  • NP_001364208.1:p.Glu814Asp
  • NP_001364209.1:p.Glu814Asp
  • LRG_98t1:c.2442G>T
  • LRG_98:g.12734G>T
  • LRG_98p1:p.Glu814Asp
  • NC_000011.9:g.36597296G>T
  • NM_000448.2:c.2442G>T
Protein change:
E814D
Links:
dbSNP: rs768860215
NCBI 1000 Genomes Browser:
rs768860215
Molecular consequence:
  • NM_000448.3:c.2442G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377277.1:c.2442G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377278.1:c.2442G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377279.1:c.2442G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377280.1:c.2442G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Combined immunodeficiency with skin granulomas
Synonyms:
Combined cellular and humoral immune defects with granulomas
Identifiers:
MONDO: MONDO:0009306; MedGen: C2673536; OMIM: 233650
Name:
Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive
Synonyms:
SCID, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-POSITIVE; Severe immunodeficiency, autosomal recessive, T-cell negative, B-cell negative, NK cell-positive; SCID, AR, T-cell negative, B-cell negative, NK cell-positive; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011086; MedGen: C1832322; Orphanet: 331206; OMIM: 601457

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001204764Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Aug 31, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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, SCV001204764.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces glutamic acid with aspartic acid at codon 814 of the RAG1 protein (p.Glu814Asp). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is present in population databases (rs768860215, ExAC 0.009%). This variant has not been reported in the literature in individuals affected with RAG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 418449). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024