2-217449530-C-T

Variant names:

• chr2-217449530-C-T
• rs11689435
• ENST00000474063.5:n.500-15414G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000474063.5(DIRC3):​n.500-15414G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00605 in 120,802 control chromosomes in the GnomAD database, including 6 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 0.0061 (6 hom., cov: 30)
• Consequence: DIRC3 ENST00000474063.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.17
• Publications: 5 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.1).
• BS2: High Homozygotes in GnomAd4 at 6 gene

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.1523-15414G>A		intron	N/A
	DIRC3	NR_186292.1		n.2762-15414G>A		intron	N/A
	DIRC3	NR_186293.1		n.1967-15414G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIRC3	ENST00000474063.5	TSL:2	n.500-15414G>A		intron	N/A
	DIRC3	ENST00000486365.6	TSL:5	n.1523-15414G>A		intron	N/A
	DIRC3	ENST00000663562.1		n.1610-15414G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00604 AC: 729 AN: 120660 Hom.: 6 Cov.: 30

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00501

Gnomad ASJ AF: 0.00895

Gnomad EAS AF: 0.0157

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000877

Gnomad OTH AF: 0.00478

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

GnomAD4 genome AF: 0.00605 AC: 731 AN: 120802 Hom.: 6 Cov.: 30 AF XY: 0.00610 AC XY: 363 AN XY: 59500

African (AFR) AF: 0.0144 AC: 509 AN: 35272

American (AMR) AF: 0.00500 AC: 66 AN: 13198

Ashkenazi Jewish (ASJ) AF: 0.00895 AC: 26 AN: 2904

East Asian (EAS) AF: 0.0158 AC: 78 AN: 4950

South Asian (SAS) AF: 0.00 AC: 0 AN: 3036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8766

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 228

European-Non Finnish (NFE) AF: 0.000878 AC: 44 AN: 50142

Other (OTH) AF: 0.00471 AC: 8 AN: 1698

Alfa AF: 0.105 Hom.: 224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.059
DANN	Benign	0.71
PhyloP100		-3.2

Splicing

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

Other links and lift over

dbSNP: rs11689435; hg19: chr2-218314253;