Genetic Variant DPH2:c.*763C>T (chr1-43973302-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001384.5(DPH2):c.*763C>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 0.569 in 152,240 control chromosomes in the GnomAD database, including 30,150 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 0.57 ( 30147 hom., cov: 35)

Exomes 𝑓: 0.75 ( 3 hom. )

Consequence

DPH2
NM_001384.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.435

Variant links:

Genes affected

DPH2 (HGNC:3004): (diphthamide biosynthesis 2) This gene is one of two human genes similar to the yeast gene dph2. The yeast gene was identified by its ability to complement a diphthamide mutant strain, and thus probably functions in diphthamide biosynthesis. Diphthamide is a post-translationally modified histidine residue present in elongation factor 2 (EF2) that is the target of diphtheria toxin ADP-ribosylation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

DPH2 links:

ENSG00000285649 (HGNC:):

ENSG00000285649 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPH2	NM_001384.5 link	c.*763C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000255108.8	NP_001375.2	Q9BQC3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPH2	ENST00000255108.8 link	c.*763C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_001384.5	ENSP00000255108.3		Q9BQC3-1

Frequencies

GnomAD3 genomes

AF:

0.569

AC:

86614

AN:

152114

Hom.:

30148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.855

Gnomad AMR

AF:

0.594

Gnomad ASJ

AF:

0.656

Gnomad EAS

AF:

0.625

Gnomad SAS

AF:

0.598

Gnomad FIN

AF:

0.773

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.770

Gnomad OTH

AF:

0.607

GnomAD4 exome

AF:

0.750

AC:

AN:

Hom.:

Cov.:

AF XY:

0.667

AC XY:

AN XY:

show subpopulations

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.500

GnomAD4 genome

AF:

0.569

AC:

86624

AN:

152232

Hom.:

30147

Cov.:

AF XY:

0.569

AC XY:

42305

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.152

Gnomad4 AMR

AF:

0.594

Gnomad4 ASJ

AF:

0.656

Gnomad4 EAS

AF:

0.625

Gnomad4 SAS

AF:

0.598

Gnomad4 FIN

AF:

0.773

Gnomad4 NFE

AF:

0.770

Gnomad4 OTH

AF:

0.607

Alfa

AF:

0.713

Hom.:

51288

Bravo

AF:

0.540

Asia WGS

AF:

0.589

AC:

2048

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.4

DANN

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over