rs2274544

Positions:

chr13-110493286-C-T

Variant summary

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

The NM_001846.4(COL4A2):c.3634+4C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0685 in 1,613,924 control chromosomes in the GnomAD database, including 5,526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.076 ( 539 hom., cov: 32)

Exomes 𝑓: 0.068 ( 4987 hom. )

Consequence

COL4A2
NM_001846.4 splice_donor_region, intron

Scores

Splicing: ADA: 0.0005183

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0630

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=-0.7).

BP6

Variant 13-110493286-C-T is Benign according to our data. Variant chr13-110493286-C-T is described in ClinVar as [Benign]. Clinvar id is 311164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110493286-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4 linkuse as main transcript	c.3634+4C>T		splice_donor_region_variant, intron_variant		ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7 linkuse as main transcript	c.3634+4C>T		splice_donor_region_variant, intron_variant		5	NM_001846.4	ENSP00000353654	P1
COL4A2	ENST00000650225.1 linkuse as main transcript	n.1289+4C>T		splice_donor_region_variant, intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0762

AC:

11590

AN:

152176

Hom.:

540

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0653

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0740

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.172

Gnomad SAS

AF:

0.198

Gnomad FIN

AF:

0.158

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0537

Gnomad OTH

AF:

0.0642

GnomAD3 exomes

AF:

0.0910

AC:

22693

AN:

249258

Hom.:

1424

AF XY:

0.0959

AC XY:

12974

AN XY:

135286

show subpopulations

Gnomad AFR exome

AF:

0.0657

Gnomad AMR exome

AF:

0.0527

Gnomad ASJ exome

AF:

0.106

Gnomad EAS exome

AF:

0.159

Gnomad SAS exome

AF:

0.190

Gnomad FIN exome

AF:

0.154

Gnomad NFE exome

AF:

0.0553

Gnomad OTH exome

AF:

0.0858

GnomAD4 exome

AF:

0.0677

AC:

99024

AN:

1461630

Hom.:

4987

Cov.:

AF XY:

0.0717

AC XY:

52110

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.0698

Gnomad4 AMR exome

AF:

0.0559

Gnomad4 ASJ exome

AF:

0.107

Gnomad4 EAS exome

AF:

0.187

Gnomad4 SAS exome

AF:

0.189

Gnomad4 FIN exome

AF:

0.153

Gnomad4 NFE exome

AF:

0.0489

Gnomad4 OTH exome

AF:

0.0782

GnomAD4 genome

AF:

0.0762

AC:

11610

AN:

152294

Hom.:

539

Cov.:

AF XY:

0.0829

AC XY:

6176

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0656

Gnomad4 AMR

AF:

0.0737

Gnomad4 ASJ

AF:

0.112

Gnomad4 EAS

AF:

0.172

Gnomad4 SAS

AF:

0.198

Gnomad4 FIN

AF:

0.158

Gnomad4 NFE

AF:

0.0537

Gnomad4 OTH

AF:

0.0650

Alfa

AF:

0.0606

Hom.:

162

Bravo

AF:

0.0639

Asia WGS

AF:

0.162

AC:

561

AN:

3474

EpiCase

AF:

0.0553

EpiControl

AF:

0.0536

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 02, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Porencephaly 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

-0.70

CADD

Benign

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00052

dbscSNV1_RF

Benign

0.054

SpliceAI score (max)

0.040

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