13-110506527-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001846.4(COL4A2):c.4515A>G(p.Pro1505Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 1,612,360 control chromosomes in the GnomAD database, including 615,302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 54015 hom., cov: 33)

Exomes 𝑓: 0.87 ( 561287 hom. )

Consequence

COL4A2
NM_001846.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -9.52

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:

COL4A2-AS1 (HGNC:40156): (COL4A2 antisense RNA 1)

COL4A2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 13-110506527-A-G is Benign according to our data. Variant chr13-110506527-A-G is described in ClinVar as [Benign]. Clinvar id is 311180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110506527-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-9.52 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4 link	c.4515A>G	p.Pro1505Pro	synonymous_variant	Exon 46 of 48	ENST00000360467.7	NP_001837.2	P08572A0A024RDW8
COL4A2-AS1	NR_046583.1 link	n.186+1120T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7 link	c.4515A>G	p.Pro1505Pro	synonymous_variant	Exon 46 of 48	5	NM_001846.4	ENSP00000353654.5		P08572

Frequencies

GnomAD3 genomes

AF:

0.840

AC:

127688

AN:

152070

Hom.:

54013

Cov.:

show subpopulations

Gnomad AFR

AF:

0.782

Gnomad AMI

AF:

0.911

Gnomad AMR

AF:

0.837

Gnomad ASJ

AF:

0.877

Gnomad EAS

AF:

0.578

Gnomad SAS

AF:

0.770

Gnomad FIN

AF:

0.807

Gnomad MID

AF:

0.921

Gnomad NFE

AF:

0.901

Gnomad OTH

AF:

0.861

GnomAD3 exomes

AF:

0.829

AC:

202816

AN:

244712

Hom.:

85221

AF XY:

0.834

AC XY:

111129

AN XY:

133274

show subpopulations

Gnomad AFR exome

AF:

0.782

Gnomad AMR exome

AF:

0.769

Gnomad ASJ exome

AF:

0.888

Gnomad EAS exome

AF:

0.576

Gnomad SAS exome

AF:

0.783

Gnomad FIN exome

AF:

0.815

Gnomad NFE exome

AF:

0.902

Gnomad OTH exome

AF:

0.860

GnomAD4 exome

AF:

0.874

AC:

1276210

AN:

1460172

Hom.:

561287

Cov.:

AF XY:

0.873

AC XY:

633832

AN XY:

726328

show subpopulations

Gnomad4 AFR exome

AF:

0.780

Gnomad4 AMR exome

AF:

0.776

Gnomad4 ASJ exome

AF:

0.889

Gnomad4 EAS exome

AF:

0.570

Gnomad4 SAS exome

AF:

0.787

Gnomad4 FIN exome

AF:

0.816

Gnomad4 NFE exome

AF:

0.901

Gnomad4 OTH exome

AF:

0.858

GnomAD4 genome

AF:

0.839

AC:

127740

AN:

152188

Hom.:

54015

Cov.:

AF XY:

0.833

AC XY:

62011

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.781

Gnomad4 AMR

AF:

0.836

Gnomad4 ASJ

AF:

0.877

Gnomad4 EAS

AF:

0.577

Gnomad4 SAS

AF:

0.770

Gnomad4 FIN

AF:

0.807

Gnomad4 NFE

AF:

0.902

Gnomad4 OTH

AF:

0.856

Alfa

AF:

0.888

Hom.:

97484

Bravo

AF:

0.838

Asia WGS

AF:

0.700

AC:

2438

AN:

3478

EpiCase

AF:

0.907

EpiControl

AF:

0.908

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 24, 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. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.6

DANN

Benign

0.50

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

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