2-217347722-C-G

Variant summary

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

The NR_026597.2(DIRC3):n.2291-19570G>C 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 0.951 in 152,246 control chromosomes in the GnomAD database, including 69,236 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 0.95 (69236 hom., cov: 32)
• Consequence: DIRC3 NR_026597.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.636

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIRC3	NR_026597.2	n.2291-19570G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIRC3	ENST00000486365.5	n.2291-19570G>C		intron_variant, non_coding_transcript_variant		5
DIRC3	ENST00000474063.5	n.1459-19570G>C		intron_variant, non_coding_transcript_variant		2
DIRC3	ENST00000663562.1	n.2378-19570G>C		intron_variant, non_coding_transcript_variant
DIRC3	ENST00000676082.1	n.1041-19570G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.951 AC: 144709 AN: 152128 Hom.: 69207 Cov.: 32

Gnomad AFR AF: 0.831

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.982

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.998

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.964

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

GnomAD4 genome AF: 0.951 AC: 144792 AN: 152246 Hom.: 69236 Cov.: 32 AF XY: 0.953 AC XY: 70980 AN XY: 74442

Gnomad4 AFR AF: 0.830

Gnomad4 AMR AF: 0.982

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.964

Alfa AF: 0.986 Hom.: 3490

Bravo AF: 0.945

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.5
Dann	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4265993; hg19: chr2-218212445;