rs10209401

Positions:

• chr2-217339958-A-C
• chr2-217339958-A-T

Variant summary

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

The NR_026597.2(DIRC3):​n.2291-11806T>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 0.764 in 152,072 control chromosomes in the GnomAD database, including 46,623 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 0.76 (46623 hom., cov: 30)
• Consequence: DIRC3 NR_026597.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.669

Genes affected

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

DIRC3-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIRC3	NR_026597.2	n.2291-11806T>G		intron_variant, non_coding_transcript_variant
DIRC3-AS1	NR_133642.1	n.1024+3377A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIRC3	ENST00000486365.5	n.2291-11806T>G		intron_variant, non_coding_transcript_variant		5
DIRC3	ENST00000474063.5	n.1459-11806T>G		intron_variant, non_coding_transcript_variant		2
DIRC3	ENST00000663562.1	n.2378-11806T>G		intron_variant, non_coding_transcript_variant
DIRC3	ENST00000676082.1	n.1041-11806T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116089 AN: 151954 Hom.: 46613 Cov.: 30

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.915

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.891

Gnomad OTH AF: 0.792

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

GnomAD4 genome AF: 0.764 AC: 116133 AN: 152072 Hom.: 46623 Cov.: 30 AF XY: 0.766 AC XY: 56918 AN XY: 74334

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.792

Gnomad4 ASJ AF: 0.888

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.915

Gnomad4 NFE AF: 0.891

Gnomad4 OTH AF: 0.791

Alfa AF: 0.871 Hom.: 111671

Bravo AF: 0.740

Asia WGS AF: 0.681 AC: 2371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.8
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: rs10209401; hg19: chr2-218204681;