Variant rs2003149 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.468

Variant links:

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]

KDSR links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
KDSR	NM_002035.4 linkuse as main transcript	c.261G>A	p.Val87=	synonymous_variant	4/10	ENST00000645214.2	NP_002026.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDSR	ENST00000645214.2 linkuse as main transcript	c.261G>A	p.Val87=	synonymous_variant	4/10		NM_002035.4	ENSP00000494352	P1	Q06136-1

Frequencies

GnomAD3 genomes

AF:

0.602

AC:

91428

AN:

151900

Hom.:

27998

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.650

AC XY:

462160

AN XY:

711350

show subpopulations

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.:

AF XY:

0.600

AC XY:

44563

AN XY:

74286

show subpopulations

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Erythrokeratodermia variabilis et progressiva 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over