2-217445617-C-T

Variant names:

• chr2-217445617-C-T
• rs966423
• ENST00000474063.5:n.500-11501G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000474063.5(DIRC3):​n.500-11501G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 152,038 control chromosomes in the GnomAD database, including 16,843 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 0.44 (16843 hom., cov: 32)
• Consequence: DIRC3 ENST00000474063.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61
• Publications: 72 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000474063.5. 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
	DIRC3	NR_026597.2		n.1523-11501G>A		intron	N/A
	DIRC3	NR_186292.1		n.2762-11501G>A		intron	N/A
	DIRC3	NR_186293.1		n.1967-11501G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIRC3	ENST00000474063.5	TSL:2	n.500-11501G>A		intron	N/A
	DIRC3	ENST00000486365.6	TSL:5	n.1523-11501G>A		intron	N/A
	DIRC3	ENST00000663562.1		n.1610-11501G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66789 AN: 151920 Hom.: 16848 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.439 AC: 66787 AN: 152038 Hom.: 16843 Cov.: 32 AF XY: 0.434 AC XY: 32267 AN XY: 74322

African (AFR) AF: 0.215 AC: 8935 AN: 41478

American (AMR) AF: 0.418 AC: 6393 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 2141 AN: 3470

East Asian (EAS) AF: 0.220 AC: 1138 AN: 5164

South Asian (SAS) AF: 0.248 AC: 1192 AN: 4816

European-Finnish (FIN) AF: 0.513 AC: 5427 AN: 10574

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39957 AN: 67938

Other (OTH) AF: 0.478 AC: 1011 AN: 2114

Alfa AF: 0.540 Hom.: 101053

Bravo AF: 0.424

Asia WGS AF: 0.204 AC: 710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.5
DANN	Benign	0.47
PhyloP100		1.6

Splicing

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

Other links and lift over

dbSNP: rs966423; hg19: chr2-218310340;