13-110473259-A-G

Variant names:

• chr13-110473259-A-G
• rs11617206
• NM_001846.4:c.2425+109A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001846.4(COL4A2):​c.2425+109A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 1,008,436 control chromosomes in the GnomAD database, including 124,147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.47 (17259 hom., cov: 34)
  • Exomes 𝑓: 0.50 (106888 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.389
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 13-110473259-A-G is Benign according to our data. Variant chr13-110473259-A-G is described in ClinVar as Benign. ClinVar VariationId is 1293760.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.492 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.2425+109A>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.2425+109A>G		intron	N/A	ENSP00000353654.5
	COL4A2	ENST00000714399.1		c.2506+109A>G		intron	N/A	ENSP00000519666.1
	COL4A2	ENST00000400163.8	TSL:5	c.2425+109A>G		intron	N/A	ENSP00000383027.4

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72187 AN: 152032 Hom.: 17244 Cov.: 34

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.496

GnomAD4 exome AF: 0.499 AC: 427139 AN: 856286 Hom.: 106888 AF XY: 0.500 AC XY: 216414 AN XY: 432594

African (AFR) AF: 0.453 AC: 8858 AN: 19566

American (AMR) AF: 0.493 AC: 10745 AN: 21784

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 9385 AN: 17594

East Asian (EAS) AF: 0.415 AC: 13255 AN: 31906

South Asian (SAS) AF: 0.495 AC: 28994 AN: 58572

European-Finnish (FIN) AF: 0.468 AC: 16542 AN: 35328

Middle Eastern (MID) AF: 0.562 AC: 1589 AN: 2828

European-Non Finnish (NFE) AF: 0.505 AC: 317788 AN: 629260

Other (OTH) AF: 0.507 AC: 19983 AN: 39448

GnomAD4 genome AF: 0.475 AC: 72238 AN: 152150 Hom.: 17259 Cov.: 34 AF XY: 0.474 AC XY: 35226 AN XY: 74352

African (AFR) AF: 0.443 AC: 18396 AN: 41498

American (AMR) AF: 0.470 AC: 7185 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1813 AN: 3468

East Asian (EAS) AF: 0.433 AC: 2232 AN: 5158

South Asian (SAS) AF: 0.494 AC: 2386 AN: 4830

European-Finnish (FIN) AF: 0.464 AC: 4908 AN: 10586

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33760 AN: 68004

Other (OTH) AF: 0.500 AC: 1058 AN: 2114

Alfa AF: 0.488 Hom.: 4803

Bravo AF: 0.475

Asia WGS AF: 0.467 AC: 1626 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 09, 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	-0.97
CADD	Benign	2.5
DANN	Benign	0.32
PhyloP100		-0.39
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: rs11617206; hg19: chr13-111125606;