17-2036598-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001383.6(DPH1):c.470C>T(p.Thr157Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00663 in 1,614,134 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0067 ( 51 hom. )

Consequence

DPH1
NM_001383.6 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.16

Variant links:

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]

DPH1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010593861).

BP6

Variant 17-2036598-C-T is Benign according to our data. Variant chr17-2036598-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 445317.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00573 (872/152312) while in subpopulation NFE AF= 0.00889 (605/68024). AF 95% confidence interval is 0.00831. There are 0 homozygotes in gnomad4. There are 399 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 51 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPH1	NM_001383.6 link	c.470C>T	p.Thr157Ile	missense_variant	Exon 5 of 13	ENST00000263083.12	NP_001374.4	Q9BZG8-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPH1	ENST00000263083.12 link	c.470C>T	p.Thr157Ile	missense_variant	Exon 5 of 13	1	NM_001383.6	ENSP00000263083.7		Q9BZG8-4

Frequencies

GnomAD3 genomes

AF:

0.00573

AC:

872

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00615

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.00377

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00889

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00596

AC:

1486

AN:

249438

Hom.:

AF XY:

0.00617

AC XY:

835

AN XY:

135368

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00374

Gnomad ASJ exome

AF:

0.0152

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00431

Gnomad FIN exome

AF:

0.00297

Gnomad NFE exome

AF:

0.00834

Gnomad OTH exome

AF:

0.00743

GnomAD4 exome

AF:

0.00672

AC:

9827

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00671

AC XY:

4883

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00382

Gnomad4 ASJ exome

AF:

0.0157

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00451

Gnomad4 FIN exome

AF:

0.00253

Gnomad4 NFE exome

AF:

0.00740

Gnomad4 OTH exome

AF:

0.00652

GnomAD4 genome

AF:

0.00573

AC:

872

AN:

152312

Hom.:

Cov.:

AF XY:

0.00536

AC XY:

399

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00614

Gnomad4 ASJ

AF:

0.0159

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.00377

Gnomad4 NFE

AF:

0.00889

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00855

Hom.:

Bravo

AF:

0.00552

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00118

AC:

ESP6500EA

AF:

0.00994

AC:

ExAC

AF:

0.00608

AC:

736

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0113

EpiControl

AF:

0.0114

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DPH1: BP4, BS2 -

Mar 07, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.15

T;.

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.83

L;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.74

N;.

REVEL

Benign

0.038

Sift

Benign

0.16

T;.

Sift4G

Benign

0.15

T;T

Polyphen

0.0010

B;.

Vest4

0.35

MVP

0.40

MPC

0.15

ClinPred

0.0089

GERP RS

4.4

Varity_R

0.059

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over