rs58124222

Variant names:

• chr13-110480600-G-A
• rs58124222
• NM_001846.4:c.2758+210G>A

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.2758+210G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,120 control chromosomes in the GnomAD database, including 3,205 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (3205 hom., cov: 33)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.416
• 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=-0.87).
• BP6: Variant 13-110480600-G-A is Benign according to our data. Variant chr13-110480600-G-A is described in ClinVar as Benign. ClinVar VariationId is 1236973.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.2758+210G>A		intron_variant	Intron 31 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.2758+210G>A		intron_variant	Intron 31 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30692 AN: 152002 Hom.: 3204 Cov.: 33

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.175

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.202 AC: 30704 AN: 152120 Hom.: 3205 Cov.: 33 AF XY: 0.199 AC XY: 14811 AN XY: 74386

African (AFR) AF: 0.267 AC: 11064 AN: 41500

American (AMR) AF: 0.152 AC: 2323 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 500 AN: 3472

East Asian (EAS) AF: 0.186 AC: 960 AN: 5172

South Asian (SAS) AF: 0.194 AC: 934 AN: 4820

European-Finnish (FIN) AF: 0.146 AC: 1544 AN: 10578

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12690 AN: 67968

Other (OTH) AF: 0.172 AC: 364 AN: 2112

Alfa AF: 0.195 Hom.: 1237

Bravo AF: 0.206

Asia WGS AF: 0.198 AC: 691 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.87
CADD	Benign	4.8
DANN	Benign	0.37
PhyloP100		0.42
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: rs58124222; hg19: chr13-111132947;