chr21-46125912-C-G

Position:

• chr21-46125912-C-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001849.4(COL6A2):​c.2097C>G​(p.Gly699Gly) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G699G) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: COL6A2 NM_001849.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP7: Synonymous conserved (PhyloP=-1.67 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL6A2	NM_001849.4	c.2097C>G	p.Gly699Gly	synonymous_variant	26/28	ENST00000300527.9	NP_001840.3
COL6A2	NM_058174.3	c.2097C>G	p.Gly699Gly	synonymous_variant	26/28		NP_478054.2
COL6A2	NM_058175.3	c.2097C>G	p.Gly699Gly	synonymous_variant	26/28		NP_478055.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A2	ENST00000300527.9	c.2097C>G	p.Gly699Gly	synonymous_variant	26/28	1	NM_001849.4	ENSP00000300527.4
COL6A2	ENST00000397763.6	c.2097C>G	p.Gly699Gly	synonymous_variant	26/28	5		ENSP00000380870.1
COL6A2	ENST00000409416.6	c.2097C>G	p.Gly699Gly	synonymous_variant	25/27	5		ENSP00000387115.1
COL6A2	ENST00000413758.1	c.*18C>G		downstream_gene_variant		3		ENSP00000395751.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 72

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.8
DANN	Benign	0.86

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: rs13046639; hg19: chr21-47545826;