rs7990383

Variant names:

Variant summary

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

The NM_001846.4(COL4A2):c.1550G>A(p.Arg517Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 1,608,274 control chromosomes in the GnomAD database, including 275,583 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 0.59 ( 27089 hom., cov: 31)

Exomes 𝑓: 0.58 ( 248494 hom. )

Consequence

COL4A2
NM_001846.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.28

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-AS2 (HGNC:39849): (COL4A2 antisense RNA 2)

COL4A2-AS2 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=1.3651943E-5).

BP6

Variant 13-110458888-G-A is Benign according to our data. Variant chr13-110458888-G-A is described in ClinVar as [Benign]. Clinvar id is 311129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110458888-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4 link	c.1550G>A	p.Arg517Lys	missense_variant	Exon 22 of 48	ENST00000360467.7	NP_001837.2	P08572A0A024RDW8
COL4A2-AS2	NR_171022.1 link	n.266-602C>T		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL4A2	ENST00000360467.7 link	c.1550G>A	p.Arg517Lys	missense_variant	Exon 22 of 48	5	NM_001846.4	ENSP00000353654.5	P08572
COL4A2	ENST00000617564.2 link	c.806G>A	p.Arg269Lys	missense_variant	Exon 10 of 10	6		ENSP00000481492.3	A0A087WY39
COL4A2-AS2	ENST00000458403.2 link	n.266-602C>T		intron_variant	Intron 1 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.586

AC:

89041

AN:

151888

Hom.:

27056

Cov.:

show subpopulations

Gnomad AFR

AF:

0.683

Gnomad AMI

AF:

0.675

Gnomad AMR

AF:

0.493

Gnomad ASJ

AF:

0.679

Gnomad EAS

AF:

0.225

Gnomad SAS

AF:

0.456

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.747

Gnomad NFE

AF:

0.603

Gnomad OTH

AF:

0.586

GnomAD3 exomes

AF:

0.524

AC:

127365

AN:

243276

Hom.:

35306

AF XY:

0.527

AC XY:

69711

AN XY:

132158

show subpopulations

Gnomad AFR exome

AF:

0.689

Gnomad AMR exome

AF:

0.389

Gnomad ASJ exome

AF:

0.666

Gnomad EAS exome

AF:

0.231

Gnomad SAS exome

AF:

0.480

Gnomad FIN exome

AF:

0.444

Gnomad NFE exome

AF:

0.602

Gnomad OTH exome

AF:

0.547

GnomAD4 exome

AF:

0.577

AC:

839972

AN:

1456268

Hom.:

248494

Cov.:

AF XY:

0.575

AC XY:

416327

AN XY:

724358

show subpopulations

Gnomad4 AFR exome

AF:

0.694

Gnomad4 AMR exome

AF:

0.397

Gnomad4 ASJ exome

AF:

0.664

Gnomad4 EAS exome

AF:

0.184

Gnomad4 SAS exome

AF:

0.479

Gnomad4 FIN exome

AF:

0.445

Gnomad4 NFE exome

AF:

0.606

Gnomad4 OTH exome

AF:

0.578

GnomAD4 genome

AF:

0.586

AC:

89128

AN:

152006

Hom.:

27089

Cov.:

AF XY:

0.574

AC XY:

42615

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.683

Gnomad4 AMR

AF:

0.492

Gnomad4 ASJ

AF:

0.679

Gnomad4 EAS

AF:

0.226

Gnomad4 SAS

AF:

0.458

Gnomad4 FIN

AF:

0.429

Gnomad4 NFE

AF:

0.603

Gnomad4 OTH

AF:

0.585

Alfa

AF:

0.604

Hom.:

18910

Bravo

AF:

0.594

TwinsUK

AF:

0.602

AC:

2234

ALSPAC

AF:

0.610

AC:

2350

ESP6500AA

AF:

0.694

AC:

2674

ESP6500EA

AF:

0.607

AC:

5007

ExAC

AF:

0.532

AC:

64271

Asia WGS

AF:

0.376

AC:

1310

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

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

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.044

DANN

Benign

0.50

DEOGEN2

Benign

0.29

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.0036

LIST_S2

Benign

0.18

MetaRNN

Benign

0.000014

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.090

PrimateAI

Benign

0.28

PROVEAN

Benign

0.41

REVEL

Uncertain

0.31

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.023

MPC

0.45

ClinPred

0.022

GERP RS

-10

Varity_R

0.083

gMVP

0.35

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