1-150966805-C-T

Variant names:

• chr1-150966805-C-T
• rs149992226
• NM_022075.5:c.799G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_022075.5(CERS2):​c.799G>A​(p.Val267Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00557 in 1,614,048 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0041 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0057 (30 hom.)
• Consequence: CERS2 NM_022075.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.256
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009523839).
• BP6: Variant 1-150966805-C-T is Benign according to our data. Variant chr1-150966805-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2639166.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 617 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERS2	NM_022075.5	c.799G>A	p.Val267Ile	missense_variant	Exon 9 of 11	ENST00000368954.10	NP_071358.1
CERS2	NM_181746.4	c.799G>A	p.Val267Ile	missense_variant	Exon 9 of 11		NP_859530.1
CERS2	XM_011509451.3	c.859G>A	p.Val287Ile	missense_variant	Exon 9 of 11		XP_011507753.1
CERS2	XM_011509452.4	c.799G>A	p.Val267Ile	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.799G>A	p.Val267Ile	missense_variant	Exon 9 of 11	1	NM_022075.5	ENSP00000357950.5

Frequencies

GnomAD3 genomes AF: 0.00406 AC: 617 AN: 152112 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000990

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00269

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00866

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00617

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00435 AC: 1093 AN: 251478 AF XY: 0.00419

Gnomad AFR exome AF: 0.000984

Gnomad AMR exome AF: 0.00194

Gnomad ASJ exome AF: 0.000794

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00919

Gnomad NFE exome AF: 0.00654

Gnomad OTH exome AF: 0.00570

GnomAD4 exome AF: 0.00573 AC: 8369 AN: 1461818 Hom.: 30 Cov.: 33 AF XY: 0.00559 AC XY: 4067 AN XY: 727222

African (AFR) AF: 0.000926 AC: 31 AN: 33480

American (AMR) AF: 0.00215 AC: 96 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000651 AC: 17 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000812 AC: 70 AN: 86256

European-Finnish (FIN) AF: 0.00870 AC: 465 AN: 53420

Middle Eastern (MID) AF: 0.00503 AC: 29 AN: 5766

European-Non Finnish (NFE) AF: 0.00658 AC: 7319 AN: 1111956

Other (OTH) AF: 0.00565 AC: 341 AN: 60390

GnomAD4 genome AF: 0.00405 AC: 617 AN: 152230 Hom.: 2 Cov.: 32 AF XY: 0.00417 AC XY: 310 AN XY: 74426

African (AFR) AF: 0.000988 AC: 41 AN: 41518

American (AMR) AF: 0.00268 AC: 41 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.00866 AC: 92 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00618 AC: 420 AN: 68014

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00548 Hom.: 4

Bravo AF: 0.00414

TwinsUK AF: 0.00809 AC: 30

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00744 AC: 64

ExAC AF: 0.00440 AC: 534

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00453

EpiControl AF: 0.00533

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CERS2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	2.8
DANN	Benign	0.86
DEOGEN2	Benign	0.30	.;T;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.68	T;T;.;T
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.0095	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.95	.;L;L;.
PhyloP100		-0.26
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.40	N;N;N;.
REVEL	Benign	0.26
Sift	Benign	1.0	T;T;T;.
Sift4G	Benign	1.0	T;T;T;.
Polyphen		0.082	.;B;B;.
Vest4		0.10
MVP		0.51
MPC		0.47
ClinPred		0.0047	T
GERP RS		-0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.027
gMVP		0.38
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs149992226; hg19: chr1-150939281; COSMIC: COSV54989012; COSMIC: COSV54989012;