1-43971407-CGC-TCA

Variant names:

• chr1-43971407-CGC-TCA
• NM_001384.5:c.505_507delCGCinsTCA
• DPH2 p.Arg169Ser

Variant summary

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

The NM_001384.5(DPH2):​c.505_507delCGCinsTCA​(p.Arg169Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R169C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DPH2 NM_001384.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.895
• 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 0 ACMG points.

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.505_507delCGCinsTCA	p.Arg169Ser	missense	N/A	NP_001375.2
	DPH2	NM_001319165.2		c.277_279delCGCinsTCA	p.Arg93Ser	missense	N/A	NP_001306094.1	B3KRB8
	DPH2	NM_001319168.2		c.277_279delCGCinsTCA	p.Arg93Ser	missense	N/A	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.505_507delCGCinsTCA	p.Arg169Ser	missense	N/A	ENSP00000255108.3	Q9BQC3-1
	DPH2	ENST00000922599.1		c.523_525delCGCinsTCA	p.Arg175Ser	missense	N/A	ENSP00000592658.1
	DPH2	ENST00000955917.1		c.505_507delCGCinsTCA	p.Arg169Ser	missense	N/A	ENSP00000625976.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.90

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-44437079;