dbSNP rs9559818: COL4A2:c.2426-124G>A (chr13-110477879-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001846.4(COL4A2):c.2426-124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 986,188 control chromosomes in the GnomAD database, including 100,125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 13995 hom., cov: 33)

Exomes 𝑓: 0.45 ( 86130 hom. )

Consequence

COL4A2
NM_001846.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.243

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 13-110477879-G-A is Benign according to our data. Variant chr13-110477879-G-A is described in ClinVar as [Benign]. Clinvar id is 1260163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4 link	c.2426-124G>A		intron_variant	Intron 29 of 47	ENST00000360467.7	NP_001837.2	P08572A0A024RDW8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL4A2	ENST00000360467.7 link	c.2426-124G>A	intron_variant	Intron 29 of 47	5	NM_001846.4	ENSP00000353654.5	P08572
COL4A2	ENST00000483683.2 link	n.-69G>A	upstream_gene_variant		2
COL4A2	ENST00000650225.1 link	n.-44G>A	upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.427

AC:

64880

AN:

151950

Hom.:

13984

Cov.:

show subpopulations

Gnomad AFR

AF:

0.376

Gnomad AMI

AF:

0.367

Gnomad AMR

AF:

0.423

Gnomad ASJ

AF:

0.490

Gnomad EAS

AF:

0.432

Gnomad SAS

AF:

0.461

Gnomad FIN

AF:

0.423

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.453

Gnomad OTH

AF:

0.452

GnomAD4 exome

AF:

0.453

AC:

378135

AN:

834122

Hom.:

86130

Cov.:

AF XY:

0.455

AC XY:

185207

AN XY:

407112

show subpopulations

Gnomad4 AFR exome

AF:

0.372

Gnomad4 AMR exome

AF:

0.419

Gnomad4 ASJ exome

AF:

0.486

Gnomad4 EAS exome

AF:

0.407

Gnomad4 SAS exome

AF:

0.465

Gnomad4 FIN exome

AF:

0.423

Gnomad4 NFE exome

AF:

0.458

Gnomad4 OTH exome

AF:

0.460

GnomAD4 genome

AF:

0.427

AC:

64929

AN:

152066

Hom.:

13995

Cov.:

AF XY:

0.426

AC XY:

31689

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.376

Gnomad4 AMR

AF:

0.422

Gnomad4 ASJ

AF:

0.490

Gnomad4 EAS

AF:

0.433

Gnomad4 SAS

AF:

0.462

Gnomad4 FIN

AF:

0.423

Gnomad4 NFE

AF:

0.453

Gnomad4 OTH

AF:

0.457

Alfa

AF:

0.433

Hom.:

2289

Bravo

AF:

0.425

Asia WGS

AF:

0.453

AC:

1577

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.7

DANN

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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