Genetic Variant COL4A2:c.1012-100C>G (chr13-110446698-C-G) – 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.1012-100C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.085 in 978,070 control chromosomes in the GnomAD database, including 4,871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.090 ( 748 hom., cov: 33)

Exomes 𝑓: 0.084 ( 4123 hom. )

Consequence

COL4A2
NM_001846.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.186

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=-0.88).

BP6

Variant 13-110446698-C-G is Benign according to our data. Variant chr13-110446698-C-G is described in ClinVar as [Benign]. Clinvar id is 1231605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4 link	c.1012-100C>G		intron_variant	Intron 17 of 47	ENST00000360467.7	NP_001837.2	P08572A0A024RDW8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL4A2	ENST00000360467.7 link	c.1012-100C>G	intron_variant	Intron 17 of 47	5	NM_001846.4	ENSP00000353654.5	P08572
COL4A2	ENST00000650540.1 link	c.1012-100C>G	intron_variant	Intron 17 of 17			ENSP00000497878.1	A0A3B3ITQ8
COL4A2	ENST00000617564.2 link	c.268-100C>G	intron_variant	Intron 5 of 9	6		ENSP00000481492.3	A0A087WY39

Frequencies

GnomAD3 genomes

AF:

0.0896

AC:

13625

AN:

152104

Hom.:

739

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0802

Gnomad AMI

AF:

0.136

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.253

Gnomad SAS

AF:

0.0535

Gnomad FIN

AF:

0.0874

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0712

Gnomad OTH

AF:

0.101

GnomAD4 exome

AF:

0.0841

AC:

69451

AN:

825848

Hom.:

4123

AF XY:

0.0818

AC XY:

34751

AN XY:

424912

show subpopulations

Gnomad4 AFR exome

AF:

0.0820

Gnomad4 AMR exome

AF:

0.177

Gnomad4 ASJ exome

AF:

0.139

Gnomad4 EAS exome

AF:

0.274

Gnomad4 SAS exome

AF:

0.0466

Gnomad4 FIN exome

AF:

0.0796

Gnomad4 NFE exome

AF:

0.0695

Gnomad4 OTH exome

AF:

0.0890

GnomAD4 genome

AF:

0.0897

AC:

13661

AN:

152222

Hom.:

748

Cov.:

AF XY:

0.0902

AC XY:

6712

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0805

Gnomad4 AMR

AF:

0.141

Gnomad4 ASJ

AF:

0.136

Gnomad4 EAS

AF:

0.252

Gnomad4 SAS

AF:

0.0533

Gnomad4 FIN

AF:

0.0874

Gnomad4 NFE

AF:

0.0712

Gnomad4 OTH

AF:

0.102

Alfa

AF:

0.0775

Hom.:

Bravo

AF:

0.0975

Asia WGS

AF:

0.132

AC:

459

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.3

DANN

Benign

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