1-43971413-C-A

Variant names:

• chr1-43971413-C-A
• rs767303260
• NM_001384.5:c.511C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001384.5(DPH2):​c.511C>A​(p.Arg171Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,706 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DPH2 NM_001384.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384.5. 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
	DPH2	NM_001384.5	MANE Select	c.511C>A	p.Arg171Arg	synonymous	Exon 4 of 6	NP_001375.2
	DPH2	NM_001319165.2		c.283C>A	p.Arg95Arg	synonymous	Exon 4 of 6	NP_001306094.1	B3KRB8
	DPH2	NM_001319168.2		c.283C>A	p.Arg95Arg	synonymous	Exon 4 of 6	NP_001306097.1	B3KRB8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPH2	ENST00000255108.8	TSL:1 MANE Select	c.511C>A	p.Arg171Arg	synonymous	Exon 4 of 6	ENSP00000255108.3	Q9BQC3-1
	DPH2	ENST00000922599.1		c.529C>A	p.Arg177Arg	synonymous	Exon 4 of 6	ENSP00000592658.1
	DPH2	ENST00000955917.1		c.511C>A	p.Arg171Arg	synonymous	Exon 4 of 6	ENSP00000625976.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446706 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 717746

African (AFR) AF: 0.00 AC: 0 AN: 32886

American (AMR) AF: 0.0000233 AC: 1 AN: 42960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25316

East Asian (EAS) AF: 0.00 AC: 0 AN: 39382

South Asian (SAS) AF: 0.00 AC: 0 AN: 85450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102274

Other (OTH) AF: 0.00 AC: 0 AN: 59560

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.86
PhyloP100		-0.48
PromoterAI		0.025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.35		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs767303260; hg19: chr1-44437085;