rs4238272

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001846.4(COL4A2):c.297G>A(p.Thr99Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.961 in 1,614,068 control chromosomes in the GnomAD database, including 745,245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.94 ( 67054 hom., cov: 31)

Exomes 𝑓: 0.96 ( 678191 hom. )

Consequence

COL4A2
NM_001846.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.795

Publications

24 publications found

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 Gene-Disease associations (from GenCC):

porencephaly 2
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
COL4A1 or COL4A2-related cerebral small vessel disease
Inheritance: AD Classification: MODERATE Submitted by: Illumina
familial porencephaly
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

COL4A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 13-110424850-G-A is Benign according to our data. Variant chr13-110424850-G-A is described in ClinVar as Benign. ClinVar VariationId is 311096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.795 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4 link	c.297G>A	p.Thr99Thr	synonymous_variant	Exon 5 of 48	ENST00000360467.7	NP_001837.2	P08572A0A024RDW8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7 link	c.297G>A	p.Thr99Thr	synonymous_variant	Exon 5 of 48	5	NM_001846.4	ENSP00000353654.5		P08572

Frequencies

GnomAD3 genomes

AF:

0.937

AC:

142587

AN:

152124

Hom.:

67015

Cov.:

show subpopulations

Gnomad AFR

AF:

0.859

Gnomad AMI

AF:

0.985

Gnomad AMR

AF:

0.964

Gnomad ASJ

AF:

0.979

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.973

Gnomad FIN

AF:

0.987

Gnomad MID

AF:

0.962

Gnomad NFE

AF:

0.961

Gnomad OTH

AF:

0.950

GnomAD2 exomes

AF:

0.964

AC:

240599

AN:

249490

AF XY:

0.965

show subpopulations

Gnomad AFR exome

AF:

0.854

Gnomad AMR exome

AF:

0.981

Gnomad ASJ exome

AF:

0.981

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.985

Gnomad NFE exome

AF:

0.961

Gnomad OTH exome

AF:

0.971

GnomAD4 exome

AF:

0.963

AC:

1407681

AN:

1461826

Hom.:

678191

Cov.:

AF XY:

0.963

AC XY:

700486

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.851

AC:

28476

AN:

33474

American (AMR)

AF:

0.981

AC:

43866

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.981

AC:

25635

AN:

26132

East Asian (EAS)

AF:

1.00

AC:

39695

AN:

39700

South Asian (SAS)

AF:

0.971

AC:

83791

AN:

86254

European-Finnish (FIN)

AF:

0.984

AC:

52559

AN:

53414

Middle Eastern (MID)

AF:

0.959

AC:

5531

AN:

5768

European-Non Finnish (NFE)

AF:

0.962

AC:

1070203

AN:

1111968

Other (OTH)

AF:

0.959

AC:

57925

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

2597

5194

7790

10387

12984

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21632

43264

64896

86528

108160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.937

AC:

142684

AN:

152242

Hom.:

67054

Cov.:

AF XY:

0.938

AC XY:

69838

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.859

AC:

35675

AN:

41542

American (AMR)

AF:

0.964

AC:

14759

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.979

AC:

3399

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5149

AN:

5152

South Asian (SAS)

AF:

0.973

AC:

4695

AN:

4824

European-Finnish (FIN)

AF:

0.987

AC:

10484

AN:

10618

Middle Eastern (MID)

AF:

0.963

AC:

283

AN:

294

European-Non Finnish (NFE)

AF:

0.961

AC:

65339

AN:

68014

Other (OTH)

AF:

0.950

AC:

2003

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

434

869

1303

1738

2172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

912

1824

2736

3648

4560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.950

Hom.:

60425

Bravo

AF:

0.934

Asia WGS

AF:

0.977

AC:

3397

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

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

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.090

(source)

DANN

Benign

0.66

PhyloP100

-0.80

PromoterAI

-0.0043

Neutral

(source)

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over