chr2-217310350-G-A

Position:

• chr2-217310350-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_026597.2(DIRC3):​n.3065+7616C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,066 control chromosomes in the GnomAD database, including 1,242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.11 (1242 hom., cov: 31)
• Consequence: DIRC3 NR_026597.2 intron, non_coding_transcript
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.665

Genes affected

DIRC3-AS1 (HGNC:50636): (DIRC3 antisense RNA 1)

DIRC3 (HGNC:17805): (disrupted in renal carcinoma 3)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIRC3	NR_026597.2	n.3065+7616C>T		intron_variant, non_coding_transcript_variant
DIRC3-AS1	NR_133642.1	n.400+7565G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIRC3-AS1	ENST00000695932.1	n.1947-7519G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17284 AN: 151948 Hom.: 1241 Cov.: 31

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0568

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0793

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.114 AC: 17306 AN: 152066 Hom.: 1242 Cov.: 31 AF XY: 0.113 AC XY: 8378 AN XY: 74312

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.0755

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.0568

Gnomad4 NFE AF: 0.0793

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0882 Hom.: 719

Bravo AF: 0.127

Asia WGS AF: 0.218 AC: 755 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Vascular endothelial growth factor (VEGF) inhibitor response Other:1

association, no assertion criteria provided

case-control

Department of Ophthalmology, College of Medicine, Hanyang University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.8
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16857280; hg19: chr2-218175073;