rs60212072

Variant names:

• chr13-110434303-G-A
• rs60212072
• NM_001846.4:c.685-98G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001846.4(COL4A2):​c.685-98G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0482 in 1,127,992 control chromosomes in the GnomAD database, including 2,257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.081 (794 hom., cov: 33)
  • Exomes 𝑓: 0.043 (1463 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.16
• Publications: 2 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 13-110434303-G-A is Benign according to our data. Variant chr13-110434303-G-A is described in ClinVar as Benign. ClinVar VariationId is 1273707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.685-98G>A		intron_variant	Intron 11 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.685-98G>A		intron_variant	Intron 11 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.0814 AC: 12385 AN: 152110 Hom.: 792 Cov.: 33

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0579

Gnomad ASJ AF: 0.0306

Gnomad EAS AF: 0.0647

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0780

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0311

Gnomad OTH AF: 0.0621

GnomAD4 exome AF: 0.0430 AC: 41964 AN: 975764 Hom.: 1463 AF XY: 0.0446 AC XY: 22473 AN XY: 503668

African (AFR) AF: 0.184 AC: 3962 AN: 21530

American (AMR) AF: 0.0417 AC: 1327 AN: 31844

Ashkenazi Jewish (ASJ) AF: 0.0276 AC: 572 AN: 20714

East Asian (EAS) AF: 0.0698 AC: 2511 AN: 35970

South Asian (SAS) AF: 0.108 AC: 7227 AN: 67042

European-Finnish (FIN) AF: 0.0712 AC: 3252 AN: 45702

Middle Eastern (MID) AF: 0.0453 AC: 204 AN: 4502

European-Non Finnish (NFE) AF: 0.0295 AC: 20757 AN: 704718

Other (OTH) AF: 0.0492 AC: 2152 AN: 43742

GnomAD4 genome AF: 0.0815 AC: 12401 AN: 152228 Hom.: 794 Cov.: 33 AF XY: 0.0836 AC XY: 6219 AN XY: 74428

African (AFR) AF: 0.179 AC: 7432 AN: 41520

American (AMR) AF: 0.0577 AC: 882 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0306 AC: 106 AN: 3468

East Asian (EAS) AF: 0.0647 AC: 335 AN: 5180

South Asian (SAS) AF: 0.112 AC: 540 AN: 4826

European-Finnish (FIN) AF: 0.0780 AC: 826 AN: 10592

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0311 AC: 2114 AN: 68026

Other (OTH) AF: 0.0615 AC: 130 AN: 2114

Alfa AF: 0.0598 Hom.: 91

Bravo AF: 0.0825

Asia WGS AF: 0.103 AC: 358 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	-0.95
CADD	Benign	0.21
DANN	Benign	0.36
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs60212072; hg19: chr13-111086650;