rs2281973

Positions:

• chr13-110478327-C-T

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.2587+163C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,102 control chromosomes in the GnomAD database, including 8,069 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.32 (8069 hom., cov: 33)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.603

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=-0.98).
• BP6: Variant 13-110478327-C-T is Benign according to our data. Variant chr13-110478327-C-T is described in ClinVar as [Benign]. Clinvar id is 1263387.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.2587+163C>T		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.2587+163C>T		intron_variant		5	NM_001846.4	P1
COL4A2	ENST00000483683.2	n.217+163C>T		intron_variant, non_coding_transcript_variant		2
COL4A2	ENST00000650225.1	n.242+163C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48964 AN: 151982 Hom.: 8055 Cov.: 33

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.322 AC: 49019 AN: 152102 Hom.: 8069 Cov.: 33 AF XY: 0.324 AC XY: 24100 AN XY: 74362

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.337

Alfa AF: 0.317 Hom.: 12919

Bravo AF: 0.321

Asia WGS AF: 0.412 AC: 1433 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.64

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: rs2281973; hg19: chr13-111130674;