dbSNP rs760263812: COL6A2:p.Arg264Ser (chr21-46114062-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001849.4(COL6A2):c.790C>A(p.Arg264Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,178 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

COL6A2
NM_001849.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.783

Variant links:

Genes affected

COL6A2 (HGNC:2212): (collagen type VI alpha 2 chain) This gene encodes one of the three alpha chains of type VI collagen, a beaded filament collagen found in most connective tissues. The product of this gene contains several domains similar to von Willebrand Factor type A domains. These domains have been shown to bind extracellular matrix proteins, an interaction that explains the importance of this collagen in organizing matrix components. Mutations in this gene are associated with Bethlem myopathy and Ullrich scleroatonic muscular dystrophy. Three transcript variants have been identified for this gene. [provided by RefSeq, Jul 2008]

COL6A2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A2	NM_001849.4 link	c.790C>A	p.Arg264Ser	missense_variant	Exon 5 of 28	ENST00000300527.9	NP_001840.3	P12110-1A0A384MDP3
COL6A2	NM_058174.3 link	c.790C>A	p.Arg264Ser	missense_variant	Exon 5 of 28		NP_478054.2	P12110-2
COL6A2	NM_058175.3 link	c.790C>A	p.Arg264Ser	missense_variant	Exon 5 of 28		NP_478055.2	P12110-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL6A2	ENST00000300527.9 link	c.790C>A	p.Arg264Ser	missense_variant	Exon 5 of 28	1	NM_001849.4	ENSP00000300527.4	P12110-1
COL6A2	ENST00000397763.6 link	c.790C>A	p.Arg264Ser	missense_variant	Exon 5 of 28	5		ENSP00000380870.1	P12110-2
COL6A2	ENST00000409416.6 link	c.790C>A	p.Arg264Ser	missense_variant	Exon 4 of 27	5		ENSP00000387115.1	P12110-3
COL6A2	ENST00000485591.1 link	n.446C>A		non_coding_transcript_exon_variant	Exon 1 of 7	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726940

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.23

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Uncertain

0.42

T;.;.;.

Eigen

Benign

0.030

Eigen_PC

Benign

0.093

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.86

D;D;.;D

M_CAP

Pathogenic

0.47

MetaRNN

Uncertain

0.71

D;D;D;D

MetaSVM

Pathogenic

0.81

MutationAssessor

Benign

1.2

L;L;L;L

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.4

N;N;N;N

REVEL

Pathogenic

0.73

Sift

Benign

0.21

T;T;T;T

Sift4G

Benign

0.17

T;T;T;T

Polyphen

0.99

D;B;B;P

Vest4

0.70

MutPred

0.42

Loss of MoRF binding (P = 0.0251);Loss of MoRF binding (P = 0.0251);Loss of MoRF binding (P = 0.0251);Loss of MoRF binding (P = 0.0251);

MVP

0.99

MPC

0.59

ClinPred

0.90

GERP RS

3.5

Varity_R

0.30

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over