rs117412802

Positions:

chr13-110491254-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001846.4(COL4A2):c.3368A>G(p.Glu1123Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,599,498 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0098 ( 13 hom., cov: 33)

Exomes 𝑓: 0.012 ( 143 hom. )

Consequence

COL4A2
NM_001846.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10O:1

Conservation

PhyloP100: 3.57

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 (HGNC:):

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 (MetaRNN=0.010744929).

BP6

Variant 13-110491254-A-G is Benign according to our data. Variant chr13-110491254-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 29629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110491254-A-G is described in Lovd as [Likely_benign]. Variant chr13-110491254-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00979 (1490/152212) while in subpopulation NFE AF= 0.0139 (946/68006). AF 95% confidence interval is 0.0132. There are 13 homozygotes in gnomad4. There are 743 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1490 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4 linkuse as main transcript	c.3368A>G	p.Glu1123Gly	missense_variant	37/48	ENST00000360467.7	NP_001837.2	P08572A0A024RDW8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7 linkuse as main transcript	c.3368A>G	p.Glu1123Gly	missense_variant	37/48	5	NM_001846.4	ENSP00000353654.5		P08572
COL4A2	ENST00000650225.1 linkuse as main transcript	n.1023A>G		non_coding_transcript_exon_variant	8/19

Frequencies

GnomAD3 genomes

AF:

0.00980

AC:

1490

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00229

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00629

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.0297

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0139

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00910

AC:

2047

AN:

224932

Hom.:

AF XY:

0.00932

AC XY:

1134

AN XY:

121716

show subpopulations

Gnomad AFR exome

AF:

0.00223

Gnomad AMR exome

AF:

0.00378

Gnomad ASJ exome

AF:

0.00293

Gnomad EAS exome

AF:

0.0000589

Gnomad SAS exome

AF:

0.00365

Gnomad FIN exome

AF:

0.0245

Gnomad NFE exome

AF:

0.0124

Gnomad OTH exome

AF:

0.0102

GnomAD4 exome

AF:

0.0121

AC:

17461

AN:

1447286

Hom.:

143

Cov.:

AF XY:

0.0119

AC XY:

8535

AN XY:

718390

show subpopulations

Gnomad4 AFR exome

AF:

0.00169

Gnomad4 AMR exome

AF:

0.00351

Gnomad4 ASJ exome

AF:

0.00337

Gnomad4 EAS exome

AF:

0.000204

Gnomad4 SAS exome

AF:

0.00362

Gnomad4 FIN exome

AF:

0.0272

Gnomad4 NFE exome

AF:

0.0134

Gnomad4 OTH exome

AF:

0.0102

GnomAD4 genome

AF:

0.00979

AC:

1490

AN:

152212

Hom.:

Cov.:

AF XY:

0.00998

AC XY:

743

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00229

Gnomad4 AMR

AF:

0.00628

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.0297

Gnomad4 NFE

AF:

0.0139

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.0111

Hom.:

Bravo

AF:

0.00725

TwinsUK

AF:

0.0146

AC:

ALSPAC

AF:

0.0138

AC:

ESP6500AA

AF:

0.00223

AC:

ESP6500EA

AF:

0.0134

AC:

112

ExAC

AF:

0.00783

AC:

945

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:7

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	COL4A2: BS1, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jan 09, 2017	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 28, 2018	This variant is associated with the following publications: (PMID: 32172663, 22209247, 25719457, 24390199) -

Porencephaly 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 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. -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

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

- -

Hemorrhage, intracerebral, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jan 13, 2012

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.71

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.52

MetaRNN

Benign

0.011

MetaSVM

Uncertain

0.25

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.4

REVEL

Uncertain

0.47

Sift

Benign

0.081

Sift4G

Benign

0.098

Polyphen

0.96

Vest4

0.77

MVP

0.93

MPC

0.88

ClinPred

0.018

GERP RS

5.0

Varity_R

0.18

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

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