rs138363207

Positions:

• chr21-46126476-T-TGGCCCGGCCCGGCCCGGCCC
• chr21-46126476-T-TGGCCCGGCCCGGCCC
• chr21-46126476-T-TGGCCC
• chr21-46126476-T-TGGCCCGGCCC
• chr21-46126476-T-TGGCCCGGCCCGGCCCGGCCCGGCCC

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_001849.4(COL6A2):​c.2423-18_2423-17insCGGCCCGGCCCGGCCCGGCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00878 in 1,610,762 control chromosomes in the GnomAD database, including 91 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0057 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0091 (85 hom.)
• Consequence: COL6A2 NM_001849.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.874

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 Benign. Variant got -12 ACMG points.

• BP6: Variant 21-46126476-T-TGGCCCGGCCCGGCCCGGCCC is Benign according to our data. Variant chr21-46126476-T-TGGCCCGGCCCGGCCCGGCCC is described in ClinVar as [Likely_benign]. Clinvar id is 420369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 6 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL6A2	NM_001849.4	c.2423-18_2423-17insCGGCCCGGCCCGGCCCGGCC		intron_variant		ENST00000300527.9	NP_001840.3
COL6A2	NM_058174.3	c.2423-18_2423-17insCGGCCCGGCCCGGCCCGGCC		intron_variant			NP_478054.2
COL6A2	NM_058175.3	c.2423-18_2423-17insCGGCCCGGCCCGGCCCGGCC		intron_variant			NP_478055.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A2	ENST00000300527.9	c.2423-18_2423-17insCGGCCCGGCCCGGCCCGGCC		intron_variant		1	NM_001849.4	ENSP00000300527.4
COL6A2	ENST00000397763.6	c.2423-18_2423-17insCGGCCCGGCCCGGCCCGGCC		intron_variant		5		ENSP00000380870.1
COL6A2	ENST00000409416.6	c.2423-18_2423-17insCGGCCCGGCCCGGCCCGGCC		intron_variant		5		ENSP00000387115.1

Frequencies

GnomAD3 genomes AF: 0.00567 AC: 862 AN: 152116 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00423

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0100

Gnomad OTH AF: 0.00621

GnomAD4 exome AF: 0.00910 AC: 13274 AN: 1458528 Hom.: 85 Cov.: 34 AF XY: 0.00876 AC XY: 6358 AN XY: 725706

Gnomad4 AFR exome AF: 0.00158

Gnomad4 AMR exome AF: 0.00206

Gnomad4 ASJ exome AF: 0.00406

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.000545

Gnomad4 FIN exome AF: 0.00362

Gnomad4 NFE exome AF: 0.0111

Gnomad4 OTH exome AF: 0.00705

GnomAD4 genome AF: 0.00566 AC: 862 AN: 152234 Hom.: 6 Cov.: 32 AF XY: 0.00535 AC XY: 398 AN XY: 74434

Gnomad4 AFR AF: 0.00188

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00423

Gnomad4 NFE AF: 0.0100

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00151 Hom.: 8

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

COL6A2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs138363207; hg19: chr21-47546390;