rs60212072

chr13-110434303-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001846.4(COL4A2):c.685-98G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0482 in 1,127,992 control chromosomes in the GnomAD database, including 2,257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.081 (794 hom., cov: 33)
  • Exomes 𝑓: 0.043 (1463 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.16

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 13-110434303-G-A is Benign according to our data. Variant chr13-110434303-G-A is described in ClinVar as [Benign]. Clinvar id is 1273707.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.685-98G>A		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.685-98G>A		intron_variant		5	NM_001846.4	P1
COL4A2	ENST00000650540.1	c.685-98G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0814 AC: 12385 AN: 152110 Hom.: 792 Cov.: 33

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0579

Gnomad ASJ AF: 0.0306

Gnomad EAS AF: 0.0647

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0780

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0311

Gnomad OTH AF: 0.0621

GnomAD4 exome AF: 0.0430 AC: 41964 AN: 975764 Hom.: 1463 AF XY: 0.0446 AC XY: 22473 AN XY: 503668

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.0417

Gnomad4 ASJ exome AF: 0.0276

Gnomad4 EAS exome AF: 0.0698

Gnomad4 SAS exome AF: 0.108

Gnomad4 FIN exome AF: 0.0712

Gnomad4 NFE exome AF: 0.0295

Gnomad4 OTH exome AF: 0.0492

GnomAD4 genome AF: 0.0815 AC: 12401 AN: 152228 Hom.: 794 Cov.: 33 AF XY: 0.0836 AC XY: 6219 AN XY: 74428

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.0577

Gnomad4 ASJ AF: 0.0306

Gnomad4 EAS AF: 0.0647

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.0780

Gnomad4 NFE AF: 0.0311

Gnomad4 OTH AF: 0.0615

Alfa AF: 0.0554 Hom.: 78

Bravo AF: 0.0825

Asia WGS AF: 0.103 AC: 358 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 09, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.21
Dann	Benign	0.36

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: rs60212072; hg19: chr13-111086650;