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NM_080680.3(COL11A2):c.4943A>T (p.His1648Leu) AND Rare genetic deafness

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 8, 2020
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:
RCV000610034.5

Allele description [Variation Report for NM_080680.3(COL11A2):c.4943A>T (p.His1648Leu)]

NM_080680.3(COL11A2):c.4943A>T (p.His1648Leu)

Gene:
COL11A2:collagen type XI alpha 2 chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6p21.32
Genomic location:
Preferred name:
NM_080680.3(COL11A2):c.4943A>T (p.His1648Leu)
HGVS:
  • NC_000006.12:g.33164394T>A
  • NG_011589.1:g.33075A>T
  • NM_080679.3:c.4622A>T
  • NM_080680.3:c.4943A>TMANE SELECT
  • NM_080681.3:c.4685A>T
  • NP_542410.2:p.His1541Leu
  • NP_542411.2:p.His1648Leu
  • NP_542411.2:p.His1648Leu
  • NP_542412.2:p.His1562Leu
  • NC_000006.11:g.33132171T>A
  • NM_080680.2:c.4943A>T
Protein change:
H1541L
Links:
dbSNP: rs1487325262
NCBI 1000 Genomes Browser:
rs1487325262
Molecular consequence:
  • NM_080679.3:c.4622A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_080680.3:c.4943A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_080681.3:c.4685A>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
2

Condition(s)

Name:
Rare genetic deafness
Identifiers:
MedGen: C5680250; Orphanet: 96210

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000713767Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Likely pathogenic
(Jun 8, 2020) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown42not providednot providednot providedclinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000713767.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided4not providednot providedclinical testing PubMed (1)

Description

The p.His1648Leu variant in COL11A2 variant has been reported by our laboratory in 2 individuals with hearing loss, including one individual in whom a likely pathogenic COL11A2 variant was confirmed in trans and both variants segregated in an affected sibling. None of the affected individuals harboring this variant were reported to have clinical features of Stickler or OSMED syndrome. The p.His1648Leu variant was absent from large population studies. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive hearing loss. ACMG/AMP Criteria applied: PM2, PM3, PP3, PP1.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided4not provided2not provided

Last Updated: Dec 24, 2023