1-26432658-A-G

Position:

• chr1-26432658-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_205861.3(DHDDS):​c.-55-233A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 473,802 control chromosomes in the GnomAD database, including 25,054 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (8596 hom., cov: 32)
  • Exomes 𝑓: 0.28 (16458 hom.)
• Consequence: DHDDS NM_205861.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0140

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 1-26432658-A-G is Benign according to our data. Variant chr1-26432658-A-G is described in ClinVar as [Benign]. Clinvar id is 1257348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHDDS	NM_205861.3	c.-55-233A>G		intron_variant		ENST00000236342.12	NP_995583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHDDS	ENST00000236342.12	c.-55-233A>G		intron_variant		1	NM_205861.3	ENSP00000236342	P4

Frequencies

GnomAD3 genomes AF: 0.309 AC: 47004 AN: 151928 Hom.: 8593 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.293

GnomAD4 exome AF: 0.282 AC: 90862 AN: 321756 Hom.: 16458 Cov.: 0 AF XY: 0.288 AC XY: 49284 AN XY: 171072

Gnomad4 AFR exome AF: 0.440

Gnomad4 AMR exome AF: 0.276

Gnomad4 ASJ exome AF: 0.205

Gnomad4 EAS exome AF: 0.755

Gnomad4 SAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.244

Gnomad4 NFE exome AF: 0.210

Gnomad4 OTH exome AF: 0.274

GnomAD4 genome AF: 0.309 AC: 47031 AN: 152046 Hom.: 8596 Cov.: 32 AF XY: 0.314 AC XY: 23328 AN XY: 74322

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.296

Alfa AF: 0.234 Hom.: 4410

Bravo AF: 0.319

Asia WGS AF: 0.548 AC: 1904 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.32		Position offset: -17

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

Publications

LitVar

Other links and lift over

dbSNP: rs3811461; hg19: chr1-26759149;