chr6-33170061-G-C
Variant summary
Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1
The NM_080680.3(COL11A2):c.3622C>G(p.Pro1208Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,613,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1208S) has been classified as Likely benign.
Frequency
Consequence
NM_080680.3 missense
Scores
Clinical Significance
Conservation
Publications
- autosomal dominant nonsyndromic hearing loss 13Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
- nonsyndromic genetic hearing lossInheritance: AD, AR Classification: DEFINITIVE, MODERATE Submitted by: ClinGen
- otospondylomegaepiphyseal dysplasia, autosomal dominantInheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, Ambry Genetics, Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
- autosomal recessive nonsyndromic hearing loss 53Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- otospondylomegaepiphyseal dysplasiaInheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
- otospondylomegaepiphyseal dysplasia, autosomal recessiveInheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
- autosomal dominant nonsyndromic hearing lossInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- fibrochondrogenesisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- hearing loss, autosomal recessiveInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Benign. The variant received -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL11A2 | NM_080680.3 | c.3622C>G | p.Pro1208Ala | missense_variant | Exon 49 of 66 | ENST00000341947.7 | NP_542411.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL11A2 | ENST00000341947.7 | c.3622C>G | p.Pro1208Ala | missense_variant | Exon 49 of 66 | 5 | NM_080680.3 | ENSP00000339915.2 | ||
COL11A2 | ENST00000374708.8 | c.3364C>G | p.Pro1122Ala | missense_variant | Exon 47 of 64 | 5 | ENSP00000363840.4 | |||
COL11A2 | ENST00000477772.1 | n.273-4245C>G | intron_variant | Intron 5 of 8 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152126Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000526 AC: 13AN: 247216 AF XY: 0.0000372 show subpopulations
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1460790Hom.: 0 Cov.: 34 AF XY: 0.0000138 AC XY: 10AN XY: 726710 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000138 AC: 21AN: 152244Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74450 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at