21-46112444-A-T

Variant names:

• chr21-46112444-A-T
• NM_001849.4:c.581A>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001849.4(COL6A2):​c.581A>T​(p.Gln194Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: COL6A2 NM_001849.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04883623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A2	NM_001849.4	c.581A>T	p.Gln194Leu	missense_variant	Exon 3 of 28	ENST00000300527.9	NP_001840.3
COL6A2	NM_058174.3	c.581A>T	p.Gln194Leu	missense_variant	Exon 3 of 28		NP_478054.2
COL6A2	NM_058175.3	c.581A>T	p.Gln194Leu	missense_variant	Exon 3 of 28		NP_478055.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A2	ENST00000300527.9	c.581A>T	p.Gln194Leu	missense_variant	Exon 3 of 28	1	NM_001849.4	ENSP00000300527.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	6.2
DANN	Benign	0.69
DEOGEN2	Benign	0.22	T;.;.;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.22	T;T;.;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.049	T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	-0.55	N;N;N;N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-2.0	N;N;N;N
REVEL	Benign	0.25
Sift	Benign	0.16	T;T;T;T
Sift4G	Benign	0.14	T;T;T;T
Polyphen		0.0	B;B;B;B
Vest4		0.12
MutPred		0.61		Loss of methylation at K197 (P = 0.0552);Loss of methylation at K197 (P = 0.0552);Loss of methylation at K197 (P = 0.0552);Loss of methylation at K197 (P = 0.0552);
MVP		0.32
MPC		0.13
ClinPred		0.27	T
GERP RS		-8.7
Varity_R		0.10
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr21-47532358; COSMIC: COSV56016681; COSMIC: COSV56016681;