13-110480209-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001846.4(COL4A2):c.2588-11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,581,508 control chromosomes in the GnomAD database, including 74,393 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6061 hom., cov: 34)

Exomes 𝑓: 0.31 ( 68332 hom. )

Consequence

COL4A2
NM_001846.4 intron

Scores

Splicing: ADA: 0.00004166

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.08

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 13-110480209-C-T is Benign according to our data. Variant chr13-110480209-C-T is described in ClinVar as [Benign]. Clinvar id is 311151.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110480209-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4 link	c.2588-11C>T		intron_variant	Intron 30 of 47	ENST00000360467.7	NP_001837.2	P08572A0A024RDW8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL4A2	ENST00000360467.7 link	c.2588-11C>T	intron_variant	Intron 30 of 47	5	NM_001846.4	ENSP00000353654.5	P08572
COL4A2	ENST00000483683.2 link	n.218-11C>T	intron_variant	Intron 1 of 2	2
COL4A2	ENST00000650225.1 link	n.243-11C>T	intron_variant	Intron 1 of 18

Frequencies

GnomAD3 genomes

AF:

0.260

AC:

39575

AN:

152078

Hom.:

6053

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0852

Gnomad AMI

AF:

0.295

Gnomad AMR

AF:

0.350

Gnomad ASJ

AF:

0.311

Gnomad EAS

AF:

0.337

Gnomad SAS

AF:

0.281

Gnomad FIN

AF:

0.390

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.315

Gnomad OTH

AF:

0.284

GnomAD3 exomes

AF:

0.308

AC:

68886

AN:

223460

Hom.:

11116

AF XY:

0.309

AC XY:

37659

AN XY:

121756

show subpopulations

Gnomad AFR exome

AF:

0.0781

Gnomad AMR exome

AF:

0.371

Gnomad ASJ exome

AF:

0.314

Gnomad EAS exome

AF:

0.323

Gnomad SAS exome

AF:

0.282

Gnomad FIN exome

AF:

0.384

Gnomad NFE exome

AF:

0.313

Gnomad OTH exome

AF:

0.317

GnomAD4 exome

AF:

0.306

AC:

436893

AN:

1429312

Hom.:

68332

Cov.:

AF XY:

0.305

AC XY:

216954

AN XY:

710270

show subpopulations

Gnomad4 AFR exome

AF:

0.0683

Gnomad4 AMR exome

AF:

0.371

Gnomad4 ASJ exome

AF:

0.315

Gnomad4 EAS exome

AF:

0.377

Gnomad4 SAS exome

AF:

0.290

Gnomad4 FIN exome

AF:

0.381

Gnomad4 NFE exome

AF:

0.306

Gnomad4 OTH exome

AF:

0.290

GnomAD4 genome

AF:

0.260

AC:

39589

AN:

152196

Hom.:

6061

Cov.:

AF XY:

0.266

AC XY:

19804

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0850

Gnomad4 AMR

AF:

0.351

Gnomad4 ASJ

AF:

0.311

Gnomad4 EAS

AF:

0.337

Gnomad4 SAS

AF:

0.281

Gnomad4 FIN

AF:

0.390

Gnomad4 NFE

AF:

0.315

Gnomad4 OTH

AF:

0.282

Alfa

AF:

0.301

Hom.:

11758

Bravo

AF:

0.247

Asia WGS

AF:

0.295

AC:

1024

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 02, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Porencephaly 2

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.6

DANN

Benign

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000042

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over