21-46122829-A-T

Variant names:

• chr21-46122829-A-T
• NM_001849.4:c.1609-46A>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.1609-46A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: COL6A2 NM_001849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.533

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 (BayesDel_noAF=-0.77).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A2	NM_001849.4	c.1609-46A>T		intron_variant	Intron 20 of 27	ENST00000300527.9	NP_001840.3
COL6A2	NM_058174.3	c.1609-46A>T		intron_variant	Intron 20 of 27		NP_478054.2
COL6A2	NM_058175.3	c.1609-46A>T		intron_variant	Intron 20 of 27		NP_478055.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A2	ENST00000300527.9	c.1609-46A>T		intron_variant	Intron 20 of 27	1	NM_001849.4	ENSP00000300527.4
COL6A2	ENST00000397763.6	c.1609-46A>T		intron_variant	Intron 20 of 27	5		ENSP00000380870.1
COL6A2	ENST00000409416.6	c.1609-46A>T		intron_variant	Intron 19 of 26	5		ENSP00000387115.1
COL6A2	ENST00000413758.1	c.232-46A>T		intron_variant	Intron 5 of 10	3		ENSP00000395751.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1412942 Hom.: 0 Cov.: 27 AF XY: 0.00000142 AC XY: 1 AN XY: 705960

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: 9.36e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.7
DANN	Benign	0.89

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: chr21-47542743;