13-110511851-T-C

Variant names:

• chr13-110511851-T-C
• rs2479426
• NM_001846.4:c.4882-83T>C

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.4882-83T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 1,591,668 control chromosomes in the GnomAD database, including 264,939 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (24780 hom., cov: 34)
  • Exomes 𝑓: 0.58 (240159 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.09
• Publications: 7 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

ENSG00000289010 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 13-110511851-T-C is Benign according to our data. Variant chr13-110511851-T-C is described in ClinVar as Benign. ClinVar VariationId is 1225142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.4882-83T>C		intron_variant	Intron 47 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.4882-83T>C		intron_variant	Intron 47 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86537 AN: 152002 Hom.: 24760 Cov.: 34

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.589

GnomAD4 exome AF: 0.575 AC: 828301 AN: 1439548 Hom.: 240159 AF XY: 0.573 AC XY: 409955 AN XY: 715796

African (AFR) AF: 0.583 AC: 18964 AN: 32554

American (AMR) AF: 0.564 AC: 23116 AN: 40976

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 15248 AN: 25602

East Asian (EAS) AF: 0.368 AC: 14334 AN: 38988

South Asian (SAS) AF: 0.490 AC: 41251 AN: 84196

European-Finnish (FIN) AF: 0.497 AC: 25075 AN: 50450

Middle Eastern (MID) AF: 0.593 AC: 2517 AN: 4244

European-Non Finnish (NFE) AF: 0.593 AC: 653703 AN: 1103056

Other (OTH) AF: 0.573 AC: 34093 AN: 59482

GnomAD4 genome AF: 0.569 AC: 86604 AN: 152120 Hom.: 24780 Cov.: 34 AF XY: 0.562 AC XY: 41812 AN XY: 74374

African (AFR) AF: 0.586 AC: 24342 AN: 41504

American (AMR) AF: 0.601 AC: 9183 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2052 AN: 3472

East Asian (EAS) AF: 0.353 AC: 1827 AN: 5174

South Asian (SAS) AF: 0.477 AC: 2300 AN: 4822

European-Finnish (FIN) AF: 0.484 AC: 5120 AN: 10578

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.587 AC: 39875 AN: 67968

Other (OTH) AF: 0.583 AC: 1232 AN: 2112

Alfa AF: 0.581 Hom.: 8715

Bravo AF: 0.579

Asia WGS AF: 0.466 AC: 1624 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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.24
DANN	Benign	0.38
PhyloP100		-1.1
Mutation Taster		=20/80	disease causing

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: rs2479426; hg19: chr13-111164198;