rs11653030

chr17-2037858-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001383.6(DPH1):c.680+902C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0682 in 152,210 control chromosomes in the GnomAD database, including 500 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 0.068 (500 hom., cov: 31)
• Consequence: DPH1 NM_001383.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPH1	NM_001383.6	c.680+902C>T		intron_variant		ENST00000263083.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPH1	ENST00000263083.12	c.680+902C>T		intron_variant		1	NM_001383.6	P1

Frequencies

GnomAD3 genomes AF: 0.0682 AC: 10377 AN: 152092 Hom.: 501 Cov.: 31

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0920

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0814

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0917

Gnomad OTH AF: 0.0607

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0682 AC: 10378 AN: 152210 Hom.: 500 Cov.: 31 AF XY: 0.0691 AC XY: 5145 AN XY: 74418

Gnomad4 AFR AF: 0.0163

Gnomad4 AMR AF: 0.0923

Gnomad4 ASJ AF: 0.0579

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0812

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.0917

Gnomad4 OTH AF: 0.0596

Alfa AF: 0.0819 Hom.: 154

Bravo AF: 0.0641

Asia WGS AF: 0.0270 AC: 94 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	2.0
Dann	Benign	0.49

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: rs11653030; hg19: chr17-1941152;