chr21-46111477-A-ATGCTCCAGGGCACC

Position:

• chr21-46111477-A-ATGCTCCAGGGCACC

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001849.4(COL6A2):​c.8_21dup​(p.Val8_?7) variant causes a frameshift, start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: COL6A2 NM_001849.4 frameshift, start_lost
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 1.55

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 12 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 260 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 21-46111477-A-ATGCTCCAGGGCACC is Pathogenic according to our data. Variant chr21-46111477-A-ATGCTCCAGGGCACC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2439448.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A2	NM_001849.4	c.8_21dup	p.Val8_?7	frameshift_variant, start_lost	2/28	ENST00000300527.9
COL6A2	NM_058174.3	c.8_21dup	p.Val8_?7	frameshift_variant, start_lost	2/28	ENST00000397763.6
LOC124905043	XR_007067910.1	n.554_555insGGTGCCCTGGAGCA		non_coding_transcript_exon_variant	1/2
COL6A2	NM_058175.3	c.8_21dup	p.Val8_?7	frameshift_variant, start_lost	2/28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A2	ENST00000300527.9	c.8_21dup	p.Val8_?7	frameshift_variant, start_lost	2/28	1	NM_001849.4	P1
COL6A2	ENST00000397763.6	c.8_21dup	p.Val8_?7	frameshift_variant, start_lost	2/28	5	NM_058174.3
COL6A2	ENST00000409416.6	c.8_21dup	p.Val8_?7	frameshift_variant, start_lost	1/27	5
COL6A2	ENST00000436769.5	c.8_21dup	p.Val8_?7	frameshift_variant, start_lost	2/3	2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Mar 06, 2022

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr21-47531391;