chr13-110469370-A-G

Variant names:

• chr13-110469370-A-G
• rs9515229
• NM_001846.4:c.2203+46A>G

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.2203+46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 1,534,760 control chromosomes in the GnomAD database, including 273,067 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (28248 hom., cov: 32)
  • Exomes 𝑓: 0.59 (244819 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.577
• Publications: 5 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=-0.9).
• BP6: Variant 13-110469370-A-G is Benign according to our data. Variant chr13-110469370-A-G is described in ClinVar as Benign. ClinVar VariationId is 1264954.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001846.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	NM_001846.4	MANE Select	c.2203+46A>G		intron	N/A	NP_001837.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	ENST00000360467.7	TSL:5 MANE Select	c.2203+46A>G		intron	N/A	ENSP00000353654.5
	COL4A2	ENST00000714399.1		c.2284+46A>G		intron	N/A	ENSP00000519666.1
	COL4A2	ENST00000400163.8	TSL:5	c.2203+46A>G		intron	N/A	ENSP00000383027.4

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91182 AN: 151922 Hom.: 28214 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.606

GnomAD2 exomes AF: 0.534 AC: 81631 AN: 152880 AF XY: 0.534

Gnomad AFR exome AF: 0.704

Gnomad AMR exome AF: 0.417

Gnomad ASJ exome AF: 0.665

Gnomad EAS exome AF: 0.301

Gnomad FIN exome AF: 0.478

Gnomad NFE exome AF: 0.614

Gnomad OTH exome AF: 0.570

GnomAD4 exome AF: 0.589 AC: 814817 AN: 1382720 Hom.: 244819 Cov.: 25 AF XY: 0.586 AC XY: 399850 AN XY: 681992

African (AFR) AF: 0.711 AC: 22207 AN: 31234

American (AMR) AF: 0.424 AC: 14982 AN: 35306

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 16451 AN: 24904

East Asian (EAS) AF: 0.249 AC: 8918 AN: 35796

South Asian (SAS) AF: 0.483 AC: 37921 AN: 78552

European-Finnish (FIN) AF: 0.479 AC: 23523 AN: 49150

Middle Eastern (MID) AF: 0.647 AC: 2629 AN: 4062

European-Non Finnish (NFE) AF: 0.614 AC: 654473 AN: 1066470

Other (OTH) AF: 0.589 AC: 33713 AN: 57246

GnomAD4 genome AF: 0.600 AC: 91275 AN: 152040 Hom.: 28248 Cov.: 32 AF XY: 0.589 AC XY: 43751 AN XY: 74340

African (AFR) AF: 0.698 AC: 28930 AN: 41436

American (AMR) AF: 0.501 AC: 7649 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2355 AN: 3472

East Asian (EAS) AF: 0.289 AC: 1497 AN: 5182

South Asian (SAS) AF: 0.464 AC: 2235 AN: 4822

European-Finnish (FIN) AF: 0.465 AC: 4910 AN: 10568

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41593 AN: 67964

Other (OTH) AF: 0.606 AC: 1279 AN: 2112

Alfa AF: 0.561 Hom.: 3168

Bravo AF: 0.606

Asia WGS AF: 0.406 AC: 1413 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

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.67
PhyloP100		-0.58
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: rs9515229; hg19: chr13-111121717;