rs76978157

Variant names:

• chr21-46129496-C-T
• rs76978157
• NM_001849.4:c.2462-2458C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_058174.3(COL6A2):​c.*5C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,561,784 control chromosomes in the GnomAD database, including 233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (17 hom., cov: 33)
  • Exomes 𝑓: 0.015 (216 hom.)
• Consequence: COL6A2 NM_058174.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.68

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 21-46129496-C-T is Benign according to our data. Variant chr21-46129496-C-T is described in ClinVar as [Benign]. Clinvar id is 262300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0125 (1900/152206) while in subpopulation AMR AF= 0.0203 (310/15286). AF 95% confidence interval is 0.0184. There are 17 homozygotes in gnomad4. There are 921 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 17 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A2	NM_001849.4	c.2462-2458C>T		intron_variant	Intron 27 of 27	ENST00000300527.9	NP_001840.3
COL6A2	NM_058174.3	c.*5C>T		3_prime_UTR_variant	Exon 28 of 28		NP_478054.2
COL6A2	NM_058175.3	c.*568C>T		3_prime_UTR_variant	Exon 28 of 28		NP_478055.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A2	ENST00000300527.9	c.2462-2458C>T		intron_variant	Intron 27 of 27	1	NM_001849.4	ENSP00000300527.4
COL6A2	ENST00000397763.6	c.*5C>T		3_prime_UTR_variant	Exon 28 of 28	5		ENSP00000380870.1
COL6A2	ENST00000409416.6	c.*568C>T		3_prime_UTR_variant	Exon 27 of 27	5		ENSP00000387115.1

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1902 AN: 152088 Hom.: 17 Cov.: 33

Gnomad AFR AF: 0.00365

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0203

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00498

Gnomad FIN AF: 0.00913

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0169

Gnomad OTH AF: 0.0206

GnomAD3 exomes AF: 0.0130 AC: 2550 AN: 196730 Hom.: 37 AF XY: 0.0135 AC XY: 1455 AN XY: 107506

Gnomad AFR exome AF: 0.00314

Gnomad AMR exome AF: 0.0118

Gnomad ASJ exome AF: 0.0137

Gnomad EAS exome AF: 0.000848

Gnomad SAS exome AF: 0.00525

Gnomad FIN exome AF: 0.00860

Gnomad NFE exome AF: 0.0195

Gnomad OTH exome AF: 0.0146

GnomAD4 exome AF: 0.0146 AC: 20565 AN: 1409578 Hom.: 216 Cov.: 31 AF XY: 0.0144 AC XY: 10041 AN XY: 695038

Gnomad4 AFR exome AF: 0.00285

Gnomad4 AMR exome AF: 0.0127

Gnomad4 ASJ exome AF: 0.0143

Gnomad4 EAS exome AF: 0.000231

Gnomad4 SAS exome AF: 0.00484

Gnomad4 FIN exome AF: 0.00814

Gnomad4 NFE exome AF: 0.0165

Gnomad4 OTH exome AF: 0.0135

GnomAD4 genome AF: 0.0125 AC: 1900 AN: 152206 Hom.: 17 Cov.: 33 AF XY: 0.0124 AC XY: 921 AN XY: 74446

Gnomad4 AFR AF: 0.00364

Gnomad4 AMR AF: 0.0203

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.00913

Gnomad4 NFE AF: 0.0169

Gnomad4 OTH AF: 0.0204

Alfa AF: 0.0143 Hom.: 3

Bravo AF: 0.0135

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.0060
DANN	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs76978157; hg19: chr21-47549410;