NM_004006.3(DMD):c.5163G>C (p.Lys1721Asn) AND not specified

Clinical significance:Likely benign (Last evaluated: Jan 4, 2021)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001290603.1

Allele description [Variation Report for NM_004006.3(DMD):c.5163G>C (p.Lys1721Asn)]

NM_004006.3(DMD):c.5163G>C (p.Lys1721Asn)

Gene:
DMD:dystrophin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xp21.1
Genomic location:
Preferred name:
NM_004006.3(DMD):c.5163G>C (p.Lys1721Asn)
HGVS:
  • NC_000023.11:g.32362950C>G
  • NG_012232.1:g.981660G>C
  • NM_000109.4:c.5139G>C
  • NM_004006.2:c.5163G>C
  • NM_004006.3:c.5163G>CMANE SELECT
  • NM_004009.3:c.5151G>C
  • NM_004010.3:c.4794G>C
  • NM_004011.4:c.1140G>C
  • NM_004012.4:c.1131G>C
  • NP_000100.3:p.Lys1713Asn
  • NP_003997.1:p.Lys1721Asn
  • NP_003997.2:p.Lys1721Asn
  • NP_004000.1:p.Lys1717Asn
  • NP_004001.1:p.Lys1598Asn
  • NP_004002.3:p.Lys380Asn
  • NP_004003.2:p.Lys377Asn
  • LRG_199t1:c.5163G>C
  • LRG_199:g.981660G>C
  • LRG_199p1:p.Lys1721Asn
  • NC_000023.10:g.32381067C>G
Protein change:
K1598N
Links:
dbSNP: rs72468630
NCBI 1000 Genomes Browser:
rs72468630
Molecular consequence:
  • NM_000109.4:c.5139G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004006.2:c.5163G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004006.3:c.5163G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004009.3:c.5151G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004010.3:c.4794G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004011.4:c.1140G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004012.4:c.1131G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001478695Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely benign
(Jan 4, 2021)
germlineclinical testing

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Genetic analysis of 1051 Chinese families with Duchenne/Becker Muscular Dystrophy.

Kong X, Zhong X, Liu L, Cui S, Yang Y, Kong L.

BMC Med Genet. 2019 Aug 14;20(1):139. doi: 10.1186/s12881-019-0873-0.

PubMed [citation]
PMID:
31412794
PMCID:
PMC6694523

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001478695.1

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

Description

Variant summary: DMD c.5163G>C (p.Lys1721Asn) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0011 in 177459 control chromosomes, predominantly at a frequency of 0.013 within the East Asian subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 1179 fold of the estimated maximal expected allele frequency for a pathogenic variant in DMD causing Dystrophinopathies phenotype (1.1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. c.5163G>C has been reported in the literature in at least an individual affected with Dystrophinopathies (e.g. Kong_2019). This report however, does not provide unequivocal conclusions about association of the variant with Dystrophinopathies. Co-occurrence with another likely pathogenic variant has been reported (DMD c.5476G>T, p.E1826X) in our internal database, providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.

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

Last Updated: Nov 6, 2021

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