rs9583500

Positions:

chr13-110469273-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.2152C>T(p.Pro718Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,602,244 control chromosomes in the GnomAD database, including 34,521 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4385 hom., cov: 32)

Exomes 𝑓: 0.20 ( 30136 hom. )

Consequence

COL4A2
NM_001846.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.924

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 (MetaRNN=0.0032528043).

BP6

Variant 13-110469273-C-T is Benign according to our data. Variant chr13-110469273-C-T is described in ClinVar as [Benign]. Clinvar id is 311145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110469273-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 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.2152C>T	p.Pro718Ser	missense_variant	28/48	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.2152C>T	p.Pro718Ser	missense_variant	28/48	5	NM_001846.4	ENSP00000353654.5		P08572
COL4A2	ENST00000494852.2 linkuse as main transcript	c.70C>T	p.Pro24Ser	missense_variant	2/4	3		ENSP00000497664.2		A0A3B3IT80

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34351

AN:

151944

Hom.:

4379

Cov.:

show subpopulations

Gnomad AFR

AF:

0.323

Gnomad AMI

AF:

0.251

Gnomad AMR

AF:

0.188

Gnomad ASJ

AF:

0.308

Gnomad EAS

AF:

0.0180

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.174

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.203

Gnomad OTH

AF:

0.237

GnomAD3 exomes

AF:

0.175

AC:

39604

AN:

226146

Hom.:

4142

AF XY:

0.173

AC XY:

21189

AN XY:

122436

show subpopulations

Gnomad AFR exome

AF:

0.324

Gnomad AMR exome

AF:

0.118

Gnomad ASJ exome

AF:

0.305

Gnomad EAS exome

AF:

0.0132

Gnomad SAS exome

AF:

0.111

Gnomad FIN exome

AF:

0.179

Gnomad NFE exome

AF:

0.204

Gnomad OTH exome

AF:

0.210

GnomAD4 exome

AF:

0.196

AC:

284844

AN:

1450182

Hom.:

30136

Cov.:

AF XY:

0.194

AC XY:

139485

AN XY:

719896

show subpopulations

Gnomad4 AFR exome

AF:

0.329

Gnomad4 AMR exome

AF:

0.127

Gnomad4 ASJ exome

AF:

0.304

Gnomad4 EAS exome

AF:

0.0107

Gnomad4 SAS exome

AF:

0.110

Gnomad4 FIN exome

AF:

0.180

Gnomad4 NFE exome

AF:

0.205

Gnomad4 OTH exome

AF:

0.205

GnomAD4 genome

AF:

0.226

AC:

34403

AN:

152062

Hom.:

4385

Cov.:

AF XY:

0.219

AC XY:

16269

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.323

Gnomad4 AMR

AF:

0.188

Gnomad4 ASJ

AF:

0.308

Gnomad4 EAS

AF:

0.0180

Gnomad4 SAS

AF:

0.103

Gnomad4 FIN

AF:

0.174

Gnomad4 NFE

AF:

0.203

Gnomad4 OTH

AF:

0.240

Alfa

AF:

0.211

Hom.:

6103

Bravo

AF:

0.234

TwinsUK

AF:

0.194

AC:

721

ALSPAC

AF:

0.203

AC:

784

ESP6500AA

AF:

0.301

AC:

1150

ESP6500EA

AF:

0.199

AC:

1637

ExAC

AF:

0.171

AC:

20572

Asia WGS

AF:

0.105

AC:

368

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 24, 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:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.60

DEOGEN2

Benign

0.29

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.086

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.0033

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.43

REVEL

Uncertain

0.30

Sift

Benign

0.83

Sift4G

Benign

0.73

Polyphen

0.21

Vest4

0.059

MPC

0.32

ClinPred

0.015

GERP RS

5.6

Varity_R

0.048

gMVP

0.14

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