rs2003149

chr18-63355558-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_002035.4(KDSR):c.261G>A(p.Val87=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,583,240 control chromosomes in the GnomAD database, including 330,186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (28005 hom., cov: 32)
  • Exomes 𝑓: 0.65 (302181 hom.)
• Consequence: KDSR NM_002035.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.468

Genes affected

KDSR (HGNC:4021): (3-ketodihydrosphingosine reductase) The protein encoded by this gene catalyzes the reduction of 3-ketodihydrosphingosine to dihydrosphingosine. The putative active site residues of the encoded protein are found on the cytosolic side of the endoplasmic reticulum membrane. A chromosomal rearrangement involving this gene is a cause of follicular lymphoma, also known as type II chronic lymphatic leukemia. The mutation of a conserved residue in the bovine ortholog causes spinal muscular atrophy. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 18-63355558-C-T is Benign according to our data. Variant chr18-63355558-C-T is described in ClinVar as [Benign]. Clinvar id is 1300062.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.468 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDSR	NM_002035.4	c.261G>A	p.Val87=	synonymous_variant	4/10	ENST00000645214.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDSR	ENST00000645214.2	c.261G>A	p.Val87=	synonymous_variant	4/10		NM_002035.4	P1

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91428 AN: 151900 Hom.: 27998 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.614

GnomAD3 exomes AF: 0.626 AC: 138800 AN: 221614 Hom.: 43715 AF XY: 0.633 AC XY: 75988 AN XY: 120106

Gnomad AFR exome AF: 0.482

Gnomad AMR exome AF: 0.621

Gnomad ASJ exome AF: 0.626

Gnomad EAS exome AF: 0.457

Gnomad SAS exome AF: 0.679

Gnomad FIN exome AF: 0.660

Gnomad NFE exome AF: 0.657

Gnomad OTH exome AF: 0.636

GnomAD4 exome AF: 0.648 AC: 928138 AN: 1431222 Hom.: 302181 Cov.: 51 AF XY: 0.650 AC XY: 462160 AN XY: 711350

Gnomad4 AFR exome AF: 0.488

Gnomad4 AMR exome AF: 0.623

Gnomad4 ASJ exome AF: 0.610

Gnomad4 EAS exome AF: 0.482

Gnomad4 SAS exome AF: 0.675

Gnomad4 FIN exome AF: 0.661

Gnomad4 NFE exome AF: 0.659

Gnomad4 OTH exome AF: 0.630

GnomAD4 genome AF: 0.602 AC: 91453 AN: 152018 Hom.: 28005 Cov.: 32 AF XY: 0.600 AC XY: 44563 AN XY: 74286

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.659

Gnomad4 FIN AF: 0.644

Gnomad4 NFE AF: 0.664

Gnomad4 OTH AF: 0.609

Alfa AF: 0.642 Hom.: 56869

Bravo AF: 0.588

Asia WGS AF: 0.544 AC: 1892 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Erythrokeratodermia variabilis et progressiva 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
Cadd	Benign	7.6
Dann	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2003149; hg19: chr18-61022791; COSMIC: COSV58506508; COSMIC: COSV58506508;