rs7984100

Positions:

• chr13-110438577-G-A
• chr13-110438577-G-C
• chr13-110438577-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001846.4(COL4A2):​c.862-41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 1,612,218 control chromosomes in the GnomAD database, including 73,930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9846 hom., cov: 33)
  • Exomes 𝑓: 0.29 (64084 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.29

Genes affected

COL4A2 (HGNC:2203): (collagen type IV alpha 2 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. The C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 13-110438577-G-A is Benign according to our data. Variant chr13-110438577-G-A is described in ClinVar as [Benign]. Clinvar id is 1217363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110438577-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.862-41G>A		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.862-41G>A		intron_variant		5	NM_001846.4	P1
COL4A2	ENST00000617564.2	c.119-41G>A		intron_variant
COL4A2	ENST00000650540.1	c.862-41G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52318 AN: 151794 Hom.: 9838 Cov.: 33

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.346

GnomAD3 exomes AF: 0.282 AC: 70299 AN: 249442 Hom.: 11100 AF XY: 0.280 AC XY: 37829 AN XY: 135330

Gnomad AFR exome AF: 0.521

Gnomad AMR exome AF: 0.193

Gnomad ASJ exome AF: 0.433

Gnomad EAS exome AF: 0.145

Gnomad SAS exome AF: 0.222

Gnomad FIN exome AF: 0.294

Gnomad NFE exome AF: 0.297

Gnomad OTH exome AF: 0.304

GnomAD4 exome AF: 0.289 AC: 422118 AN: 1460306 Hom.: 64084 Cov.: 33 AF XY: 0.287 AC XY: 208704 AN XY: 726538

Gnomad4 AFR exome AF: 0.517

Gnomad4 AMR exome AF: 0.205

Gnomad4 ASJ exome AF: 0.427

Gnomad4 EAS exome AF: 0.116

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.289

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.310

GnomAD4 genome AF: 0.345 AC: 52357 AN: 151912 Hom.: 9846 Cov.: 33 AF XY: 0.339 AC XY: 25192 AN XY: 74254

Gnomad4 AFR AF: 0.508

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.347

Alfa AF: 0.262 Hom.: 1392

Bravo AF: 0.359

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Porencephaly 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.010
DANN	Benign	0.61

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: rs7984100; hg19: chr13-111090924; COSMIC: COSV64631991;