2-217406996-T-C

Variant names:

• chr2-217406996-T-C
• rs6759952
• ENST00000474063.5:n.1458+18306A>G

Variant summary

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

The ENST00000474063.5(DIRC3):​n.1458+18306A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,314 control chromosomes in the GnomAD database, including 18,626 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 0.48 (18626 hom., cov: 29)
• Consequence: DIRC3 ENST00000474063.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141
• Publications: 26 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=-0.91).
• 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.2290+18306A>G		intron	N/A
	DIRC3	NR_186292.1		n.3529+18306A>G		intron	N/A
	DIRC3	NR_186293.1		n.2734+18306A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIRC3	ENST00000474063.5	TSL:2	n.1458+18306A>G		intron	N/A
	DIRC3	ENST00000486365.6	TSL:5	n.2290+18306A>G		intron	N/A
	DIRC3	ENST00000663562.1		n.2377+18306A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.481 AC: 72664 AN: 151196 Hom.: 18626 Cov.: 29

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.480 AC: 72693 AN: 151314 Hom.: 18626 Cov.: 29 AF XY: 0.472 AC XY: 34855 AN XY: 73852

African (AFR) AF: 0.368 AC: 15192 AN: 41230

American (AMR) AF: 0.431 AC: 6560 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2090 AN: 3470

East Asian (EAS) AF: 0.232 AC: 1183 AN: 5102

South Asian (SAS) AF: 0.202 AC: 967 AN: 4788

European-Finnish (FIN) AF: 0.497 AC: 5147 AN: 10352

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39900 AN: 67852

Other (OTH) AF: 0.507 AC: 1069 AN: 2108

Alfa AF: 0.549 Hom.: 90053

Bravo AF: 0.471

Asia WGS AF: 0.198 AC: 690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.63
PhyloP100		0.14

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6759952;

hg19: chr2-218271719;