chr17-2042450-C-T

Position:

• chr17-2042450-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000571710.6(DPH1):​c.*593C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,290,948 control chromosomes in the GnomAD database, including 20,977 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1932 hom., cov: 32)
  • Exomes 𝑓: 0.18 (19045 hom.)
• Consequence: DPH1 ENST00000571710.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.289

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 17-2042450-C-T is Benign according to our data. Variant chr17-2042450-C-T is described in ClinVar as [Benign]. Clinvar id is 1302089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPH1	NM_001383.6	c.*19-155C>T		intron_variant		ENST00000263083.12	NP_001374.4
OVCA2	NM_080822.3	c.185-155C>T		intron_variant		ENST00000572195.3	NP_543012.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPH1	ENST00000263083.12	c.*19-155C>T		intron_variant		1	NM_001383.6	ENSP00000263083	P1
OVCA2	ENST00000572195.3	c.185-155C>T		intron_variant		1	NM_080822.3	ENSP00000461388	P1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21630 AN: 152088 Hom.: 1932 Cov.: 32

Gnomad AFR AF: 0.0472

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.0582

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.175

GnomAD4 exome AF: 0.176 AC: 199886 AN: 1138742 Hom.: 19045 Cov.: 17 AF XY: 0.175 AC XY: 97041 AN XY: 555894

Gnomad4 AFR exome AF: 0.0394

Gnomad4 AMR exome AF: 0.120

Gnomad4 ASJ exome AF: 0.244

Gnomad4 EAS exome AF: 0.0387

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.210

Gnomad4 NFE exome AF: 0.186

Gnomad4 OTH exome AF: 0.180

GnomAD4 genome AF: 0.142 AC: 21629 AN: 152206 Hom.: 1932 Cov.: 32 AF XY: 0.142 AC XY: 10550 AN XY: 74410

Gnomad4 AFR AF: 0.0472

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.0583

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.175

Alfa AF: 0.176 Hom.: 533

Bravo AF: 0.135

Asia WGS AF: 0.101 AC: 352 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 29, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.4
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs55801908; hg19: chr17-1945744;