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NM_002485.5(NBN):c.1312A>G (p.Ser438Gly) AND Microcephaly, normal intelligence and immunodeficiency

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jul 6, 2022
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV001063253.9

Allele description [Variation Report for NM_002485.5(NBN):c.1312A>G (p.Ser438Gly)]

NM_002485.5(NBN):c.1312A>G (p.Ser438Gly)

Gene:
NBN:nibrin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
8q21.3
Genomic location:
Preferred name:
NM_002485.5(NBN):c.1312A>G (p.Ser438Gly)
HGVS:
  • NC_000008.11:g.89955368T>C
  • NG_008860.1:g.34304A>G
  • NM_001024688.3:c.1066A>G
  • NM_002485.5:c.1312A>GMANE SELECT
  • NP_001019859.1:p.Ser356Gly
  • NP_002476.2:p.Ser438Gly
  • NP_002476.2:p.Ser438Gly
  • LRG_158t1:c.1312A>G
  • LRG_158:g.34304A>G
  • LRG_158p1:p.Ser438Gly
  • NC_000008.10:g.90967596T>C
  • NM_002485.4:c.1312A>G
Protein change:
S356G
Links:
dbSNP: rs1456827107
NCBI 1000 Genomes Browser:
rs1456827107
Molecular consequence:
  • NM_001024688.3:c.1066A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002485.5:c.1312A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Microcephaly, normal intelligence and immunodeficiency (NBS)
Synonyms:
IMMUNODEFICIENCY, MICROCEPHALY, AND CHROMOSOMAL INSTABILITY; SEEMANOVA SYNDROME II; Nijmegen breakage syndrome; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009623; MedGen: C0398791; Orphanet: 647; OMIM: 251260

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001228091Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jul 6, 2022) 		germlineclinical testing

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

SCV002045924Genome-Nilou Lab
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Nov 7, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

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 Invitae, SCV001228091.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 480043). This variant has not been reported in the literature in individuals affected with NBN-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 438 of the NBN protein (p.Ser438Gly).

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

From Genome-Nilou Lab, SCV002045924.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 20, 2024