1-26432282-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000434391.6(DHDDS):c.-150G>A variant causes a 5 prime UTR, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,676 control chromosomes in the GnomAD database, including 8,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (8592 hom., cov: 32)
  • Exomes 𝑓: 0.26 (30 hom.)
• Consequence: DHDDS ENST00000434391.6 5_prime_UTR, NMD_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.217

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]

LOC124903883 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 1-26432282-G-A is Benign according to our data. Variant chr1-26432282-G-A is described in ClinVar as [Benign]. Clinvar id is 297068.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHDDS	NM_205861.3			upstream_gene_variant		ENST00000236342.12
LOC124903883	XR_007065557.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHDDS	ENST00000236342.12			upstream_gene_variant		1	NM_205861.3	P4

Frequencies

GnomAD3 genomes AF: 0.309 AC: 47001 AN: 152020 Hom.: 8589 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.293

GnomAD4 exome AF: 0.257 AC: 138 AN: 538 Hom.: 30 Cov.: 0 AF XY: 0.285 AC XY: 97 AN XY: 340

Gnomad4 AMR exome AF: 0.231

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.410

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.198

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.309 AC: 47028 AN: 152138 Hom.: 8592 Cov.: 32 AF XY: 0.314 AC XY: 23328 AN XY: 74388

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.721

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.297

Alfa AF: 0.247 Hom.: 916

Bravo AF: 0.319

Asia WGS AF: 0.544 AC: 1892 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Retinitis pigmentosa Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	12
Dann	Benign	0.92

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6656196; hg19: chr1-26758773; COSMIC: COSV52577791;