chr17-2042400-C-T

Position:

• chr17-2042400-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.*543C>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 0.173 in 1,255,722 control chromosomes in the GnomAD database, including 20,588 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1965 hom., cov: 32)
  • Exomes 𝑓: 0.18 (18623 hom.)
• Consequence: DPH1 ENST00000571710.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0540

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 17-2042400-C-T is Benign according to our data. Variant chr17-2042400-C-T is described in ClinVar as [Benign]. Clinvar id is 1302080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPH1	NM_001383.6	c.*19-205C>T		intron_variant		ENST00000263083.12	NP_001374.4
OVCA2	NM_080822.3	c.184+169C>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.*19-205C>T		intron_variant		1	NM_001383.6	ENSP00000263083	P1
OVCA2	ENST00000572195.3	c.184+169C>T		intron_variant		1	NM_080822.3	ENSP00000461388	P1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21947 AN: 152042 Hom.: 1966 Cov.: 32

Gnomad AFR AF: 0.0526

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.0593

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.177

GnomAD4 exome AF: 0.178 AC: 195917 AN: 1103562 Hom.: 18623 Cov.: 17 AF XY: 0.176 AC XY: 94329 AN XY: 536020

Gnomad4 AFR exome AF: 0.0475

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.245

Gnomad4 EAS exome AF: 0.0381

Gnomad4 SAS exome AF: 0.100

Gnomad4 FIN exome AF: 0.209

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.181

GnomAD4 genome AF: 0.144 AC: 21942 AN: 152160 Hom.: 1965 Cov.: 32 AF XY: 0.144 AC XY: 10723 AN XY: 74390

Gnomad4 AFR AF: 0.0525

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.0594

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.175

Alfa AF: 0.177 Hom.: 536

Bravo AF: 0.137

Asia WGS AF: 0.0970 AC: 338 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 29, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.5
DANN	Benign	0.61

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: rs55815331; hg19: chr17-1945694;