18-63362764-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002035.4(KDSR):c.198+15T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00059 in 1,568,982 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00033 (7 hom.)
• Consequence: KDSR NM_002035.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0180

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 18-63362764-A-G is Benign according to our data. Variant chr18-63362764-A-G is described in ClinVar as [Benign]. Clinvar id is 1646336.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDSR	NM_002035.4	c.198+15T>C		intron_variant		ENST00000645214.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDSR	ENST00000645214.2	c.198+15T>C		intron_variant			NM_002035.4	P1

Frequencies

GnomAD3 genomes AF: 0.00289 AC: 440 AN: 152194 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00982

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.000828 AC: 206 AN: 248910 Hom.: 1 AF XY: 0.000654 AC XY: 88 AN XY: 134620

Gnomad AFR exome AF: 0.0113

Gnomad AMR exome AF: 0.000443

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000548

Gnomad SAS exome AF: 0.0000334

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.000988

GnomAD4 exome AF: 0.000328 AC: 464 AN: 1416670 Hom.: 7 Cov.: 24 AF XY: 0.000307 AC XY: 217 AN XY: 707400

Gnomad4 AFR exome AF: 0.0106

Gnomad4 AMR exome AF: 0.000317

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000760

Gnomad4 SAS exome AF: 0.0000472

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000373

Gnomad4 OTH exome AF: 0.00161

GnomAD4 genome AF: 0.00303 AC: 461 AN: 152312 Hom.: 7 Cov.: 32 AF XY: 0.00301 AC XY: 224 AN XY: 74466

Gnomad4 AFR AF: 0.0102

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00165 Hom.: 2

Bravo AF: 0.00346

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 27, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.33
Dann	Benign	0.30

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

Publications

LitVar

Other links and lift over

dbSNP: rs138217888; hg19: chr18-61029997;