rs369491663

Variant names:

• chr1-150966808-T-A
• rs369491663
• NM_022075.5:c.796A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-150966808-T-A
• chr1-150966808-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022075.5(CERS2):​c.796A>T​(p.Ile266Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I266V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CERS2 NM_022075.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.95

Genes affected

CERS2 (HGNC:14076): (ceramide synthase 2) This gene encodes a protein that has sequence similarity to yeast longevity assurance gene 1. Mutation or overexpression of the related gene in yeast has been shown to alter yeast lifespan. The human protein may play a role in the regulation of cell growth. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERS2	NM_022075.5	c.796A>T	p.Ile266Phe	missense_variant	Exon 9 of 11	ENST00000368954.10	NP_071358.1
CERS2	NM_181746.4	c.796A>T	p.Ile266Phe	missense_variant	Exon 9 of 11		NP_859530.1
CERS2	XM_011509451.3	c.856A>T	p.Ile286Phe	missense_variant	Exon 9 of 11		XP_011507753.1
CERS2	XM_011509452.4	c.796A>T	p.Ile266Phe	missense_variant	Exon 9 of 11		XP_011507754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERS2	ENST00000368954.10	c.796A>T	p.Ile266Phe	missense_variant	Exon 9 of 11	1	NM_022075.5	ENSP00000357950.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Uncertain	0.71	.;D;D;.
Eigen	Benign	-0.12
Eigen_PC	Benign	0.037
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	T;D;.;T
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.73	D;D;D;D
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.7	.;L;L;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-2.2	N;N;N;.
REVEL	Uncertain	0.64
Sift	Benign	0.33	T;T;T;.
Sift4G	Benign	0.25	T;T;T;.
Polyphen		0.097	.;B;B;.
Vest4		0.71
MutPred		0.68		.;Loss of MoRF binding (P = 0.3388);Loss of MoRF binding (P = 0.3388);Loss of MoRF binding (P = 0.3388);
MVP		0.89
MPC		1.9
ClinPred		0.94	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.22
gMVP		0.82

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: rs369491663; hg19: chr1-150939284;