chr21-46111185-G-T

Position:

• chr21-46111185-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001849.4(COL6A2):​c.-27-265G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0263 in 152,230 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.026 (109 hom., cov: 33)
• Consequence: COL6A2 NM_001849.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.17

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 21-46111185-G-T is Benign according to our data. Variant chr21-46111185-G-T is described in ClinVar as [Benign]. Clinvar id is 1289874.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0263 (4001/152230) while in subpopulation NFE AF= 0.0299 (2035/68006). AF 95% confidence interval is 0.0288. There are 109 homozygotes in gnomad4. There are 2136 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 109 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A2	NM_001849.4	c.-27-265G>T		intron_variant		ENST00000300527.9
COL6A2	NM_058174.3	c.-27-265G>T		intron_variant		ENST00000397763.6
LOC124905043	XR_007067910.1	n.847C>A		non_coding_transcript_exon_variant	1/2
COL6A2	NM_058175.3	c.-27-265G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A2	ENST00000300527.9	c.-27-265G>T		intron_variant		1	NM_001849.4	P1
COL6A2	ENST00000397763.6	c.-27-265G>T		intron_variant		5	NM_058174.3
COL6A2	ENST00000436769.5	c.-27-265G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0263 AC: 4003 AN: 152112 Hom.: 109 Cov.: 33

Gnomad AFR AF: 0.00418

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0222

Gnomad ASJ AF: 0.0740

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00623

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0299

Gnomad OTH AF: 0.0215

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0263 AC: 4001 AN: 152230 Hom.: 109 Cov.: 33 AF XY: 0.0287 AC XY: 2136 AN XY: 74410

Gnomad4 AFR AF: 0.00416

Gnomad4 AMR AF: 0.0222

Gnomad4 ASJ AF: 0.0740

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00644

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.0299

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.0141 Hom.: 7

Bravo AF: 0.0201

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.31
DANN	Benign	0.73

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: rs112710668; hg19: chr21-47531099;