Genetic Variant NM_002035.4:c.-69A>G (chr18-63367187-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002035.4(KDSR):c.-69A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KDSR
NM_002035.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.549

Publications

15 publications found

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:

KDSR-DT (HGNC:55299): (KDSR divergent transcript)

KDSR-DT links:

LOC124904317 (HGNC:):

LOC124904317 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
KDSR	NM_002035.4 link	c.-69A>G	5_prime_UTR_variant	Exon 1 of 10	ENST00000645214.2	NP_002026.1	Q06136-1A0A024R292
KDSR-DT	NR_186602.1 link	n.-137T>C	upstream_gene_variant
LOC124904317	XR_007066400.1 link	n.-187A>G	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDSR	ENST00000645214.2 link	c.-69A>G		5_prime_UTR_variant	Exon 1 of 10		NM_002035.4	ENSP00000494352.1		Q06136-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

634550

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

307862

African (AFR)

AF:

0.00

AC:

AN:

12776

American (AMR)

AF:

0.00

AC:

AN:

6796

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10120

East Asian (EAS)

AF:

0.00

AC:

AN:

21884

South Asian (SAS)

AF:

0.00

AC:

AN:

10914

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31636

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2160

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

511006

Other (OTH)

AF:

0.00

AC:

AN:

27258

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

980

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

-0.55

PromoterAI

0.14

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over