rs9521782

Positions:

• chr13-110458696-G-A
• chr13-110458696-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.1433-75G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 1,581,270 control chromosomes in the GnomAD database, including 267,971 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25349 hom., cov: 31)
  • Exomes 𝑓: 0.57 (242622 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.54

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]

COL4A2-AS2 (HGNC:39849): (COL4A2 antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 13-110458696-G-A is Benign according to our data. Variant chr13-110458696-G-A is described in ClinVar as [Benign]. Clinvar id is 1291185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.1433-75G>A		intron_variant		ENST00000360467.7
COL4A2-AS2	NR_171022.1	n.266-410C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.1433-75G>A		intron_variant		5	NM_001846.4	P1
COL4A2-AS2	ENST00000458403.2	n.266-410C>T		intron_variant, non_coding_transcript_variant		2
COL4A2	ENST00000617564.2	c.690-75G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86259 AN: 151372 Hom.: 25324 Cov.: 31

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.579

GnomAD4 exome AF: 0.575 AC: 821924 AN: 1429780 Hom.: 242622 AF XY: 0.573 AC XY: 407464 AN XY: 711038

Gnomad4 AFR exome AF: 0.639

Gnomad4 AMR exome AF: 0.391

Gnomad4 ASJ exome AF: 0.663

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.477

Gnomad4 FIN exome AF: 0.445

Gnomad4 NFE exome AF: 0.605

Gnomad4 OTH exome AF: 0.574

GnomAD4 genome AF: 0.570 AC: 86335 AN: 151490 Hom.: 25349 Cov.: 31 AF XY: 0.557 AC XY: 41241 AN XY: 74022

Gnomad4 AFR AF: 0.628

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.578

Alfa AF: 0.599 Hom.: 4019

Bravo AF: 0.577

Asia WGS AF: 0.371 AC: 1291 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.096
DANN	Benign	0.55

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: rs9521782; hg19: chr13-111111043; COSMIC: COSV64632006; COSMIC: COSV64632006;