NM_205861.3:c.6A>G

Variant names:

• chr1-26432951-A-G
• rs2124329360
• NM_205861.3:c.6A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_205861.3(DHDDS):​c.6A>G​(p.Ser2Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DHDDS NM_205861.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.42
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 1-26432951-A-G is Benign according to our data. Variant chr1-26432951-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1639325.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.42 with no splicing effect.

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.6A>G	p.Ser2Ser	synonymous	Exon 2 of 9	NP_995583.1	Q86SQ9-1
	DHDDS	NM_024887.4		c.6A>G	p.Ser2Ser	synonymous	Exon 2 of 9	NP_079163.2
	DHDDS	NM_001243564.2		c.6A>G	p.Ser2Ser	synonymous	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.6A>G	p.Ser2Ser	synonymous	Exon 2 of 9	ENSP00000236342.7	Q86SQ9-1
	DHDDS	ENST00000526219.5	TSL:1	c.6A>G	p.Ser2Ser	synonymous	Exon 2 of 8	ENSP00000434219.1	Q86SQ9-3
	DHDDS	ENST00000434391.6	TSL:1	n.6A>G		non_coding_transcript_exon	Exon 2 of 9	ENSP00000403529.2	Q5T0A0

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely benign

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
BayesDel_noAF	Benign	-0.47
CADD	Benign	13
DANN	Benign	0.85
PhyloP100		2.4
PromoterAI		0.088	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=89/11	polymorphism

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: rs2124329360; hg19: chr1-26759442;