rs1555330577

Variant names:

• chr13-110462397-A-G
• rs1555330577
• NM_001846.4:c.1776+13A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001846.4(COL4A2):​c.1776+13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.97
• Publications: 0 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-AS2 (HGNC:39849): (COL4A2 antisense RNA 2)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	NM_001846.4	MANE Select	c.1776+13A>G		intron	N/A	NP_001837.2	P08572
	COL4A2-AS2	NR_171022.1		n.265+626T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	ENST00000360467.7	TSL:5 MANE Select	c.1776+13A>G		intron	N/A	ENSP00000353654.5	P08572
	COL4A2	ENST00000714399.1		c.1857+13A>G		intron	N/A	ENSP00000519666.1	A0AAQ5BHW7
	COL4A2	ENST00000400163.8	TSL:5	c.1776+13A>G		intron	N/A	ENSP00000383027.4	P08572

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459558 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726156

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111670

Other (OTH) AF: 0.00 AC: 0 AN: 60314

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Vasculitis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.043
DANN	Benign	0.26
PhyloP100		-2.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs1555330577; hg19: chr13-111114744;