rs11653030

Variant names:

• chr17-2037858-C-T
• rs11653030
• NM_001383.6:c.680+902C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• developmental delay with short stature, dysmorphic facial features, and sparse hair

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• developmental delay with short stature, dysmorphic facial features, and sparse hair 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• craniofacial dysplasia-short stature-ectodermal anomalies-intellectual disability syndrome

  Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001383.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPH1	NM_001383.6	MANE Select	c.680+902C>T		intron	N/A	NP_001374.4	Q9BZG8-4
	DPH1	NM_001346574.1		c.695+902C>T		intron	N/A	NP_001333503.1
	DPH1	NM_001346575.1		c.662+902C>T		intron	N/A	NP_001333504.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPH1	ENST00000263083.12	TSL:1 MANE Select	c.680+902C>T		intron	N/A	ENSP00000263083.7	Q9BZG8-4
	DPH1	ENST00000575667.6	TSL:1	n.567+902C>T		intron	N/A	ENSP00000460431.2	A0A0A0MTR4
	DPH1	ENST00000674200.2		c.695+902C>T		intron	N/A	ENSP00000501368.1	Q9BZG8-1

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

African (AFR) AF: 0.0163 AC: 678 AN: 41534

American (AMR) AF: 0.0923 AC: 1410 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0579 AC: 201 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5182

South Asian (SAS) AF: 0.0812 AC: 392 AN: 4826

European-Finnish (FIN) AF: 0.114 AC: 1205 AN: 10596

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0917 AC: 6236 AN: 67998

Other (OTH) AF: 0.0596 AC: 126 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.0
DANN	Benign	0.49
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11653030; hg19: chr17-1941152;