rs78829338

Positions:

chr13-110469223-A-G

Variant summary

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

The NM_001846.4(COL4A2):c.2102A>G(p.Lys701Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00495 in 1,591,600 control chromosomes in the GnomAD database, including 331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0087 ( 43 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 288 hom. )

Consequence

COL4A2
NM_001846.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.29

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=0.0040277243).

BP6

Variant 13-110469223-A-G is Benign according to our data. Variant chr13-110469223-A-G is described in ClinVar as [Benign]. Clinvar id is 235684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110469223-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0577 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.2102A>G	p.Lys701Arg	missense_variant	28/48	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.2102A>G	p.Lys701Arg	missense_variant	28/48	5	NM_001846.4	ENSP00000353654	P1
COL4A2	ENST00000494852.2 linkuse as main transcript	c.23A>G	p.Lys8Arg	missense_variant	2/4	3		ENSP00000497664

Frequencies

GnomAD3 genomes

AF:

0.00860

AC:

1309

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0602

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.0168

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.0139

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000661

Gnomad OTH

AF:

0.00862

GnomAD3 exomes

AF:

0.0190

AC:

3994

AN:

210576

Hom.:

216

AF XY:

0.0156

AC XY:

1773

AN XY:

113598

show subpopulations

Gnomad AFR exome

AF:

0.00163

Gnomad AMR exome

AF:

0.108

Gnomad ASJ exome

AF:

0.00316

Gnomad EAS exome

AF:

0.0145

Gnomad SAS exome

AF:

0.00237

Gnomad FIN exome

AF:

0.0124

Gnomad NFE exome

AF:

0.000549

Gnomad OTH exome

AF:

0.0127

GnomAD4 exome

AF:

0.00456

AC:

6563

AN:

1439360

Hom.:

288

Cov.:

AF XY:

0.00428

AC XY:

3053

AN XY:

713512

show subpopulations

Gnomad4 AFR exome

AF:

0.00124

Gnomad4 AMR exome

AF:

0.104

Gnomad4 ASJ exome

AF:

0.00313

Gnomad4 EAS exome

AF:

0.0180

Gnomad4 SAS exome

AF:

0.00294

Gnomad4 FIN exome

AF:

0.0115

Gnomad4 NFE exome

AF:

0.000302

Gnomad4 OTH exome

AF:

0.00423

GnomAD4 genome

AF:

0.00866

AC:

1319

AN:

152240

Hom.:

Cov.:

AF XY:

0.00974

AC XY:

725

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00173

Gnomad4 AMR

AF:

0.0609

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.0164

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.0139

Gnomad4 NFE

AF:

0.000662

Gnomad4 OTH

AF:

0.00853

Alfa

AF:

0.00423

Hom.:

Bravo

AF:

0.0138

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000780

AC:

ESP6500EA

AF:

0.000607

AC:

ExAC

AF:

0.0123

AC:

1473

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jan 13, 2016	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 01, 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. -

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

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

Eigen

Benign

0.10

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0040

MetaSVM

Uncertain

-0.20

MutationAssessor

Benign

-0.010

MutationTaster

Benign

0.55

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.33

Sift

Benign

0.40

Sift4G

Benign

0.31

Polyphen

0.96

Vest4

0.045

MPC

0.37

ClinPred

0.038

GERP RS

5.3

Varity_R

0.11

gMVP

0.30

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