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NM_000393.5(COL5A2):c.2963C>T (p.Thr988Met) AND not specified

Germline classification:
Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:
Jun 18, 2024
Review status:
criteria provided, conflicting classifications
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:
RCV000199854.20

Allele description [Variation Report for NM_000393.5(COL5A2):c.2963C>T (p.Thr988Met)]

NM_000393.5(COL5A2):c.2963C>T (p.Thr988Met)

Gene:
COL5A2:collagen type V alpha 2 chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q32.2
Genomic location:
Preferred name:
NM_000393.5(COL5A2):c.2963C>T (p.Thr988Met)
Other names:
p.T988M:ACG>ATG
HGVS:
  • NC_000002.12:g.189050645G>A
  • NG_011799.3:g.179657C>T
  • NM_000393.5:c.2963C>TMANE SELECT
  • NP_000384.2:p.Thr988Met
  • LRG_738t1:c.2963C>T
  • LRG_738:g.179657C>T
  • LRG_738p1:p.Thr988Met
  • NC_000002.11:g.189915371G>A
  • NG_011799.2:g.134235C>T
  • NM_000393.3:c.2963C>T
Protein change:
T988M
Links:
dbSNP: rs369072636
NCBI 1000 Genomes Browser:
rs369072636
Molecular consequence:
  • NM_000393.5:c.2963C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000603203ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)		Uncertain significance
(Oct 9, 2016) 		germlineclinical testing

Citation Link,

SCV005204691Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely benign
(Jun 18, 2024) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Rare functional genetic variants in COL7A1, COL6A5, COL1A2 and COL5A2 frequently occur in Chiari Malformation Type 1.

Urbizu A, Garrett ME, Soldano K, Drechsel O, Loth D, Marcé-Grau A, Mestres I Soler O, Poca MA, Ossowski S, Macaya A, Loth F, Labuda R, Ashley-Koch A.

PLoS One. 2021;16(5):e0251289. doi: 10.1371/journal.pone.0251289.

PubMed [citation]
PMID:
33974636
PMCID:
PMC8112708

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000603203.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005204691.1

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

Description

Variant summary: COL5A2 c.2963C>T (p.Thr988Met) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6.3e-05 in 158048 control chromosomes (gnomAD). The observed variant frequency is approximately 10 fold of the estimated maximal expected allele frequency for a pathogenic variant in COL5A2 causing Ehlers-Danlos Syndrome phenotype (6.3e-06). c.2963C>T has been reported in the literature in a Chiari 1 malformation cohort without patient information (Urbizu_2021). This report does not provide unequivocal conclusions about association of the variant with Ehlers-Danlos Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 33974636). ClinVar contains an entry for this variant (Variation ID: 213112). 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: Oct 26, 2024