chr1-43973302-C-T

Variant names:

• chr1-43973302-C-T
• rs7161
• NM_001384.5:c.*763C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435
• Publications: 28 publications found

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]

ENSG00000285649 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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	c.*763C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000255108.8	NP_001375.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86614 AN: 152114 Hom.: 30148 Cov.: 35

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: 6 AN: 8 Hom.: 3 Cov.: 0 AF XY: 0.667 AC XY: 4 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 4 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.569 AC: 86624 AN: 152232 Hom.: 30147 Cov.: 35 AF XY: 0.569 AC XY: 42305 AN XY: 74414

African (AFR) AF: 0.152 AC: 6310 AN: 41536

American (AMR) AF: 0.594 AC: 9079 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2279 AN: 3472

East Asian (EAS) AF: 0.625 AC: 3233 AN: 5176

South Asian (SAS) AF: 0.598 AC: 2885 AN: 4826

European-Finnish (FIN) AF: 0.773 AC: 8196 AN: 10598

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.770 AC: 52399 AN: 68016

Other (OTH) AF: 0.607 AC: 1284 AN: 2114

Alfa AF: 0.693 Hom.: 137353

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
PhyloP100		-0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs7161; hg19: chr1-44438974;