NM_001849.4:c.288C>G

Variant names:

• chr21-46112151-C-G
• NM_001849.4:c.288C>G

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001849.4(COL6A2):​c.288C>G​(p.Tyr96*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: COL6A2 NM_001849.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73

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]

LOC124905043 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• 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	c.288C>G	p.Tyr96*	stop_gained	Exon 3 of 28	ENST00000300527.9	NP_001840.3
COL6A2	NM_058174.3	c.288C>G	p.Tyr96*	stop_gained	Exon 3 of 28		NP_478054.2
COL6A2	NM_058175.3	c.288C>G	p.Tyr96*	stop_gained	Exon 3 of 28		NP_478055.2
LOC124905043	XR_007067910.1	n.-120G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A2	ENST00000300527.9	c.288C>G	p.Tyr96*	stop_gained	Exon 3 of 28	1	NM_001849.4	ENSP00000300527.4
COL6A2	ENST00000397763.6	c.288C>G	p.Tyr96*	stop_gained	Exon 3 of 28	5		ENSP00000380870.1
COL6A2	ENST00000409416.6	c.288C>G	p.Tyr96*	stop_gained	Exon 2 of 27	5		ENSP00000387115.1
COL6A2	ENST00000436769.5	c.288C>G	p.Tyr96*	stop_gained	Exon 3 of 3	2		ENSP00000390418.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460750 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726662

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.55
CADD	Pathogenic	33
DANN	Uncertain	0.99
Eigen	Benign	0.098
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.16	N
Vest4		0.75
GERP RS		0.036

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr21-47532065;