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NM_006904.7(PRKDC):c.9943T>C (p.Tyr3315His) AND Severe combined immunodeficiency due to DNA-PKcs deficiency

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 16, 2019
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:
RCV001231633.3

Allele description [Variation Report for NM_006904.7(PRKDC):c.9943T>C (p.Tyr3315His)]

NM_006904.7(PRKDC):c.9943T>C (p.Tyr3315His)

Gene:
PRKDC:protein kinase, DNA-activated, catalytic subunit [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
8q11.21
Genomic location:
Preferred name:
NM_006904.7(PRKDC):c.9943T>C (p.Tyr3315His)
HGVS:
  • NC_000008.11:g.47800966A>G
  • NG_023435.1:g.164218T>C
  • NM_001081640.2:c.9943T>C
  • NM_006904.7:c.9943T>CMANE SELECT
  • NP_001075109.1:p.Tyr3315His
  • NP_008835.5:p.Tyr3315His
  • LRG_162t1:c.9943T>C
  • LRG_162:g.164218T>C
  • NC_000008.10:g.48713527A>G
  • NM_006904.6:c.9943T>C
Protein change:
Y3315H
Links:
dbSNP: rs2087094692
NCBI 1000 Genomes Browser:
rs2087094692
Molecular consequence:
  • NM_001081640.2:c.9943T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006904.7:c.9943T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Severe combined immunodeficiency due to DNA-PKcs deficiency
Synonyms:
IMMUNODEFICIENCY 26 WITH NEUROLOGIC ABNORMALITIES; Immunodeficiency 26 with or without neurologic abnormalities
Identifiers:
MONDO: MONDO:0014423; MedGen: C4014833; OMIM: 615966

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001404161Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jul 16, 2019) 		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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001404161.3

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

Description

This variant has not been reported in the literature in individuals with PRKDC-related conditions. 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with histidine at codon 3315 of the PRKDC protein (p.Tyr3315His). The tyrosine residue is highly conserved and there is a moderate physicochemical difference between tyrosine and histidine.

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

Last Updated: Feb 20, 2024