rs121912942

Positions:

• chr21-46126535-C-G
• chr21-46126535-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001849.4(COL6A2):​c.2455C>G​(p.Gln819Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q819Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: COL6A2 NM_001849.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.91

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32051298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A2	NM_001849.4	c.2455C>G	p.Gln819Glu	missense_variant	27/28	ENST00000300527.9
COL6A2	NM_058174.3	c.2455C>G	p.Gln819Glu	missense_variant	27/28	ENST00000397763.6
COL6A2	NM_058175.3	c.2455C>G	p.Gln819Glu	missense_variant	27/28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A2	ENST00000300527.9	c.2455C>G	p.Gln819Glu	missense_variant	27/28	1	NM_001849.4	P1
COL6A2	ENST00000397763.6	c.2455C>G	p.Gln819Glu	missense_variant	27/28	5	NM_058174.3
COL6A2	ENST00000409416.6	c.2455C>G	p.Gln819Glu	missense_variant	26/27	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Benign	0.92
DEOGEN2	Benign	0.18	T;.;.;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.069
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D;D;.;D
M_CAP	Uncertain	0.096	D
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Benign	0.90	L;L;L;L
MutationTaster	Benign	0.99	D;D;D;D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.82	N;N;N;N
REVEL	Uncertain	0.41
Sift	Benign	0.084	T;T;T;T
Sift4G	Benign	0.44	T;T;T;T
Polyphen		0.0	B;P;P;P
Vest4		0.53
MutPred		0.34		Loss of catalytic residue at Q819 (P = 0.043);Loss of catalytic residue at Q819 (P = 0.043);Loss of catalytic residue at Q819 (P = 0.043);Loss of catalytic residue at Q819 (P = 0.043);
MVP		0.86
MPC		0.16
ClinPred		0.68	D
GERP RS		3.9
Varity_R		0.32
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs121912942; hg19: chr21-47546449;