2-217310749-A-G

Position:

• chr2-217310749-A-G

Variant summary

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

The ENST00000474063.5(DIRC3):​n.2233+7217T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 152,140 control chromosomes in the GnomAD database, including 41,644 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.74 (41644 hom., cov: 33)
• Consequence: DIRC3 ENST00000474063.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.887

Genes affected

DIRC3-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIRC3	NR_026597.2	n.3065+7217T>C		intron_variant
DIRC3-AS1	NR_133642.1	n.400+7964A>G		intron_variant
DIRC3	NR_186292.1	n.4304+7217T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIRC3-AS1	ENST00000452813.1	n.394+7964A>G		intron_variant		3
DIRC3	ENST00000474063.5	n.2233+7217T>C		intron_variant		2
DIRC3	ENST00000654616.2	n.1220+7217T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111987 AN: 152022 Hom.: 41622 Cov.: 33

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.804

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.742

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

GnomAD4 genome AF: 0.736 AC: 112051 AN: 152140 Hom.: 41644 Cov.: 33 AF XY: 0.738 AC XY: 54859 AN XY: 74384

Gnomad4 AFR AF: 0.660

Gnomad4 AMR AF: 0.723

Gnomad4 ASJ AF: 0.834

Gnomad4 EAS AF: 0.731

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.804

Gnomad4 NFE AF: 0.774

Gnomad4 OTH AF: 0.742

Alfa AF: 0.765 Hom.: 88039

Bravo AF: 0.724

Asia WGS AF: 0.685 AC: 2384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.091
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4141835; hg19: chr2-218175472;