NM_205861.3:c.1_2delAT

Variant names:

• chr1-26432944-CTA-C
• NM_205861.3:c.1_2delAT

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_205861.3(DHDDS):​c.1_2delAT​(p.Met1fs) variant causes a frameshift, start lost change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DHDDS NM_205861.3 frameshift, start_lost
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.55
• Publications: 0 publications found

Genes affected

DHDDS (HGNC:20603): (dehydrodolichyl diphosphate synthase subunit) The protein encoded by this gene catalyzes cis-prenyl chain elongation to produce the polyprenyl backbone of dolichol, a glycosyl carrier lipid required for the biosynthesis of several classes of glycoproteins. Mutations in this gene are associated with retinitis pigmentosa type 59. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

DHDDS-AS1 (HGNC:40925): (DHDDS antisense RNA 1)

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 35 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_205861.3. 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
	DHDDS	NM_205861.3	MANE Select	c.1_2delAT	p.Met1fs	frameshift start_lost	Exon 2 of 9	NP_995583.1	Q86SQ9-1
	DHDDS	NM_024887.4		c.1_2delAT	p.Met1fs	frameshift start_lost	Exon 2 of 9	NP_079163.2
	DHDDS	NM_001243564.2		c.1_2delAT	p.Met1fs	frameshift start_lost	Exon 2 of 8	NP_001230493.1	Q86SQ9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHDDS	ENST00000236342.12	TSL:1 MANE Select	c.1_2delAT	p.Met1fs	frameshift start_lost	Exon 2 of 9	ENSP00000236342.7	Q86SQ9-1
	DHDDS	ENST00000526219.5	TSL:1	c.1_2delAT	p.Met1fs	frameshift start_lost	Exon 2 of 8	ENSP00000434219.1	Q86SQ9-3
	DHDDS	ENST00000434391.6	TSL:1	n.1_2delAT		non_coding_transcript_exon	Exon 2 of 9	ENSP00000403529.2	Q5T0A0

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Retinitis pigmentosa 59 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.5

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

hg19: chr1-26759435;