17-2042745-C-T

Variant names:

• chr17-2042745-C-T
• rs750380507
• NM_080822.3:c.325C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_080822.3(OVCA2):​c.325C>T​(p.Leu109Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: OVCA2 NM_080822.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

Genes affected

OVCA2 (HGNC:24203): (OVCA2 serine hydrolase domain containing) Involved in response to retinoic acid. Located in cytoplasm. Biomarker of ovarian cancer. [provided by Alliance of Genome Resources, Apr 2022]

DPH1 (HGNC:3003): (diphthamide biosynthesis 1) The protein encoded by this gene is an enzyme involved in the biosynthesis of diphthamide, a modified histidine found only in elongation factor-2 (EEF2). Diphthamide residues in EEF2 are targeted for ADP-ribosylation by diphtheria toxin and Pseudomonas exotoxin A. Defects in this gene have been associated with both ovarian cancer and autosomal recessive intellectual disability with short stature, craniofacial, and ectodermal anomalies. [provided by RefSeq, Oct 2016]

ENSG00000262533 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OVCA2	NM_080822.3	c.325C>T	p.Leu109Leu	synonymous_variant	Exon 2 of 2	ENST00000572195.3	NP_543012.1
DPH1	NM_001383.6	c.*159C>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000263083.12	NP_001374.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OVCA2	ENST00000572195.3	c.325C>T	p.Leu109Leu	synonymous_variant	Exon 2 of 2	1	NM_080822.3	ENSP00000461388.1
DPH1	ENST00000263083.12	c.*159C>T		3_prime_UTR_variant	Exon 13 of 13	1	NM_001383.6	ENSP00000263083.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	15
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.47		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.47		Position offset: -2

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

Publications

LitVar

Other links and lift over

dbSNP: rs750380507; hg19: chr17-1946039;