chr13-110457114-A-ACCCCAGGCGTCCGTGGGGCTGATGCCGTGCG

Position:

• chr13-110457114-A-ACCCCAGGCGTCCGTGGGGCTGATGCCGTGCG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001846.4(COL4A2):​c.1340-229_1340-228insCCCCAGGCGTCCGTGGGGCTGATGCCGTGCG variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (52 hom., cov: 8)
  • Exomes 𝑓: 0.013 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.48

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

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 13-110457114-A-ACCCCAGGCGTCCGTGGGGCTGATGCCGTGCG is Benign according to our data. Variant chr13-110457114-A-ACCCCAGGCGTCCGTGGGGCTGATGCCGTGCG is described in ClinVar as [Benign]. Clinvar id is 1251338.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0143 (527/36908) while in subpopulation AMR AF= 0.0382 (145/3798). AF 95% confidence interval is 0.0331. There are 52 homozygotes in gnomad4. There are 249 alleles in male gnomad4 subpopulation. Median coverage is 8. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 527 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.1340-229_1340-228insCCCCAGGCGTCCGTGGGGCTGATGCCGTGCG		intron_variant		ENST00000360467.7	NP_001837.2
COL4A2-AS2	NR_171022.1	n.803_804insCGCACGGCATCAGCCCCACGGACGCCTGGGG		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.1340-229_1340-228insCCCCAGGCGTCCGTGGGGCTGATGCCGTGCG		intron_variant		5	NM_001846.4	ENSP00000353654.5
COL4A2	ENST00000617564.2	c.596-229_596-228insCCCCAGGCGTCCGTGGGGCTGATGCCGTGCG		intron_variant		6		ENSP00000481492.3
COL4A2-AS2	ENST00000458403.2	n.803_804insCGCACGGCATCAGCCCCACGGACGCCTGGGG		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 527 AN: 36870 Hom.: 52 Cov.: 8

Gnomad AFR AF: 0.00690

Gnomad AMI AF: 0.0221

Gnomad AMR AF: 0.0384

Gnomad ASJ AF: 0.0185

Gnomad EAS AF: 0.0196

Gnomad SAS AF: 0.0113

Gnomad FIN AF: 0.00451

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.0143

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0133 AC: 2677 AN: 201774 Hom.: 3 Cov.: 0 AF XY: 0.0126 AC XY: 1447 AN XY: 114920

Gnomad4 AFR exome AF: 0.00656

Gnomad4 AMR exome AF: 0.0374

Gnomad4 ASJ exome AF: 0.0127

Gnomad4 EAS exome AF: 0.0134

Gnomad4 SAS exome AF: 0.0177

Gnomad4 FIN exome AF: 0.0104

Gnomad4 NFE exome AF: 0.00988

Gnomad4 OTH exome AF: 0.0135

GnomAD4 genome AF: 0.0143 AC: 527 AN: 36908 Hom.: 52 Cov.: 8 AF XY: 0.0141 AC XY: 249 AN XY: 17720

Gnomad4 AFR AF: 0.00675

Gnomad4 AMR AF: 0.0382

Gnomad4 ASJ AF: 0.0185

Gnomad4 EAS AF: 0.0196

Gnomad4 SAS AF: 0.0113

Gnomad4 FIN AF: 0.00451

Gnomad4 NFE AF: 0.0130

Gnomad4 OTH AF: 0.0142

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 04, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs746278410; hg19: chr13-111109461;