6-33167839-G-A
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_080680.3(COL11A2):c.3974C>T(p.Ser1325Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000315 in 1,612,898 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S1325S) has been classified as Likely benign.
Frequency
Consequence
NM_080680.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL11A2 | NM_080680.3 | c.3974C>T | p.Ser1325Leu | missense_variant | 55/66 | ENST00000341947.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL11A2 | ENST00000341947.7 | c.3974C>T | p.Ser1325Leu | missense_variant | 55/66 | 5 | NM_080680.3 | P4 | |
COL11A2 | ENST00000374708.8 | c.3716C>T | p.Ser1239Leu | missense_variant | 53/64 | 5 | A1 | ||
COL11A2 | ENST00000477772.1 | n.273-2023C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.000256 AC: 39AN: 152096Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000666 AC: 164AN: 246208Hom.: 2 AF XY: 0.000827 AC XY: 111AN XY: 134244
GnomAD4 exome AF: 0.000321 AC: 469AN: 1460684Hom.: 7 Cov.: 33 AF XY: 0.000433 AC XY: 315AN XY: 726666
GnomAD4 genome AF: 0.000256 AC: 39AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.000403 AC XY: 30AN XY: 74416
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 22, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 05, 2017 | The p.Ser1325Leu variant (rs543145528) has not been reported in the medical literature, nor is it found in ClinVar. The p.Ser1325Leu variant is listed in the Genome Aggregation Database (gnomAD) browser with an allele frequency of 0.44% in the South Asian population (identified in 134 out of 30,530 chromosomes; 2 homozygotes). Additionally, the serine at codon 1325 is weakly conserved considering 11 species (Alamut software v2.9.0), and computational analyses suggest that this variant does not affect the COL11A2 protein structure/function (SIFT: tolerated, PolyPhen2: benign, MutationTaster: polymorphism). Therefore, based on the available evidence, the p.Ser1325Leu variant appears to be an ethnic-specific polymorphism present in the South Asian population and is classified as likely benign. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Connective tissue disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Jun 01, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at