chr21-46111471-G-T

Position:

• chr21-46111471-G-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP6

The ENST00000300527.9(COL6A2):​c.-6G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 30)
• Consequence: COL6A2 ENST00000300527.9 5_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0620

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 21-46111471-G-T is Benign according to our data. Variant chr21-46111471-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3054140.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL6A2	NM_001849.4	c.-6G>T		5_prime_UTR_variant	2/28	ENST00000300527.9	NP_001840.3
COL6A2	NM_058174.3	c.-6G>T		5_prime_UTR_variant	2/28	ENST00000397763.6	NP_478054.2
LOC124905043	XR_007067910.1	n.561C>A		non_coding_transcript_exon_variant	1/2
COL6A2	NM_058175.3	c.-6G>T		5_prime_UTR_variant	2/28		NP_478055.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A2	ENST00000300527.9	c.-6G>T		5_prime_UTR_variant	2/28	1	NM_001849.4	ENSP00000300527	P1
COL6A2	ENST00000397763.6	c.-6G>T		5_prime_UTR_variant	2/28	5	NM_058174.3	ENSP00000380870
COL6A2	ENST00000436769.5	c.-6G>T		5_prime_UTR_variant	2/3	2		ENSP00000390418
COL6A2	ENST00000409416.6			upstream_gene_variant		5		ENSP00000387115

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

COL6A2-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 06, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs757279009; hg19: chr21-47531385;