2-217407175-T-C

Position:

• chr2-217407175-T-C

Variant summary

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

The NR_026597.2(DIRC3):​n.2290+18127A>G 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 0.245 in 152,000 control chromosomes in the GnomAD database, including 5,264 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 0.25 (5264 hom., cov: 31)
• Consequence: DIRC3 NR_026597.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370

Genes affected

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIRC3	NR_026597.2	n.2290+18127A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIRC3	ENST00000486365.5	n.2290+18127A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37243 AN: 151882 Hom.: 5251 Cov.: 31

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.245 AC: 37302 AN: 152000 Hom.: 5264 Cov.: 31 AF XY: 0.254 AC XY: 18850 AN XY: 74284

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.260

Alfa AF: 0.221 Hom.: 5766

Bravo AF: 0.250

Asia WGS AF: 0.542 AC: 1883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.3
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1351164; hg19: chr2-218271898;