13-110457271-G-GATGCCCTGCGTCTGCGTGGGACCCCAGGCGTCCGTGGGGCTCATGCCCTGCGTCTGCGTGGGACCCCAGGCGTCCGTGGGGCTC

Position:

• chr13-110457271-G-GATGCCCTGCGTCTGCGTGGGACCCCAGGCGTCCGTGGGGCTCATGCCCTGCGTCTGCGTGGGACCCCAGGCGTCCGTGGGGCTC

Variant summary

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

The NM_001846.4(COL4A2):​c.1340-21_1340-20insGTCTGCGTGGGACCCCAGGCGTCCGTGGGGCTCATGCCCTGCGTCTGCGTGGGACCCCAGGCGTCCGTGGGGCTCATGCCCTGC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000915 in 52,442 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00092 (0 hom., cov: 30)
  • Exomes 𝑓: 0.025 (805 hom.)
  • Failed GnomAD Quality Control
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.294

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 13-110457271-G-GATGCCCTGCGTCTGCGTGGGACCCCAGGCGTCCGTGGGGCTCATGCCCTGCGTCTGCGTGGGACCCCAGGCGTCCGTGGGGCTC is Benign according to our data. Variant chr13-110457271-G-GATGCCCTGCGTCTGCGTGGGACCCCAGGCGTCCGTGGGGCTCATGCCCTGCGTCTGCGTGGGACCCCAGGCGTCCGTGGGGCTC is described in ClinVar as [Likely_benign]. Clinvar id is 1190694.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000915 (48/52442) while in subpopulation NFE AF= 0.00106 (24/22642). AF 95% confidence interval is 0.00073. There are 0 homozygotes in gnomad4. There are 24 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 48 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.1340-21_1340-20insGTCTGCGTGGGACCCCAGGCGTCCGTGGGGCTCATGCCCTGCGTCTGCGTGGGACCCCAGGCGTCCGTGGGGCTCATGCCCTGC		intron_variant		ENST00000360467.7	NP_001837.2
COL4A2-AS2	NR_171022.1	n.646_647insGAGCCCCACGGACGCCTGGGGTCCCACGCAGACGCAGGGCATGAGCCCCACGGACGCCTGGGGTCCCACGCAGACGCAGGGCAT		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.1340-21_1340-20insGTCTGCGTGGGACCCCAGGCGTCCGTGGGGCTCATGCCCTGCGTCTGCGTGGGACCCCAGGCGTCCGTGGGGCTCATGCCCTGC		intron_variant		5	NM_001846.4	ENSP00000353654.5
COL4A2	ENST00000617564.2	c.596-21_596-20insGTCTGCGTGGGACCCCAGGCGTCCGTGGGGCTCATGCCCTGCGTCTGCGTGGGACCCCAGGCGTCCGTGGGGCTCATGCCCTGC		intron_variant		6		ENSP00000481492.3
COL4A2-AS2	ENST00000458403.2	n.646_647insGAGCCCCACGGACGCCTGGGGTCCCACGCAGACGCAGGGCATGAGCCCCACGGACGCCTGGGGTCCCACGCAGACGCAGGGCAT		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.000897 AC: 47 AN: 52412 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000879

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000505

Gnomad ASJ AF: 0.00193

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000549

Gnomad FIN AF: 0.00114

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00106

Gnomad OTH AF: 0.00137

GnomAD3 exomes AF: 0.0188 AC: 994 AN: 52774 Hom.: 71 AF XY: 0.0185 AC XY: 503 AN XY: 27202

Gnomad AFR exome AF: 0.0617

Gnomad AMR exome AF: 0.0102

Gnomad ASJ exome AF: 0.0294

Gnomad EAS exome AF: 0.00346

Gnomad SAS exome AF: 0.0102

Gnomad FIN exome AF: 0.00161

Gnomad NFE exome AF: 0.0326

Gnomad OTH exome AF: 0.0231

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0248 AC: 5784 AN: 233312 Hom.: 805 Cov.: 7 AF XY: 0.0231 AC XY: 2926 AN XY: 126468

Gnomad4 AFR exome AF: 0.0380

Gnomad4 AMR exome AF: 0.00615

Gnomad4 ASJ exome AF: 0.0362

Gnomad4 EAS exome AF: 0.000727

Gnomad4 SAS exome AF: 0.0235

Gnomad4 FIN exome AF: 0.00929

Gnomad4 NFE exome AF: 0.0331

Gnomad4 OTH exome AF: 0.0277

GnomAD4 genome AF: 0.000915 AC: 48 AN: 52442 Hom.: 0 Cov.: 30 AF XY: 0.000926 AC XY: 24 AN XY: 25914

Gnomad4 AFR AF: 0.000877

Gnomad4 AMR AF: 0.000671

Gnomad4 ASJ AF: 0.00193

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000551

Gnomad4 FIN AF: 0.00114

Gnomad4 NFE AF: 0.00106

Gnomad4 OTH AF: 0.00136

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 27, 2018

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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: rs759253067; hg19: chr13-111109618;