14-77562460-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004863.4(SPTLC2):c.786T>C(p.Asn262Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.917 in 1,613,902 control chromosomes in the GnomAD database, including 682,406 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 55355 hom., cov: 32)

Exomes 𝑓: 0.92 ( 627051 hom. )

Consequence

SPTLC2
NM_004863.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.570

Variant links:

Genes affected

SPTLC2 (HGNC:11278): (serine palmitoyltransferase long chain base subunit 2) This gene encodes a long chain base subunit of serine palmitoyltransferase. Serine palmitoyltransferase, which consists of two different subunits, is the key enzyme in sphingolipid biosynthesis. It catalyzes the pyridoxal-5-prime-phosphate-dependent condensation of L-serine and palmitoyl-CoA to 3-oxosphinganine. Mutations in this gene were identified in patients with hereditary sensory neuropathy type I. [provided by RefSeq, Mar 2011]

SPTLC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 14-77562460-A-G is Benign according to our data. Variant chr14-77562460-A-G is described in ClinVar as [Benign]. Clinvar id is 314672.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-77562460-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.57 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTLC2	NM_004863.4 link	c.786T>C	p.Asn262Asn	synonymous_variant	Exon 6 of 12	ENST00000216484.7	NP_004854.1	O15270A0A024R6H1
SPTLC2	XM_011537384.3 link	c.786T>C	p.Asn262Asn	synonymous_variant	Exon 6 of 10		XP_011535686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTLC2	ENST00000216484.7 link	c.786T>C	p.Asn262Asn	synonymous_variant	Exon 6 of 12	1	NM_004863.4	ENSP00000216484.2		O15270

Frequencies

GnomAD3 genomes

AF:

0.842

AC:

127992

AN:

152080

Hom.:

55335

Cov.:

show subpopulations

Gnomad AFR

AF:

0.622

Gnomad AMI

AF:

0.969

Gnomad AMR

AF:

0.824

Gnomad ASJ

AF:

0.960

Gnomad EAS

AF:

0.990

Gnomad SAS

AF:

0.960

Gnomad FIN

AF:

0.944

Gnomad MID

AF:

0.965

Gnomad NFE

AF:

0.934

Gnomad OTH

AF:

0.877

GnomAD3 exomes

AF:

0.904

AC:

227343

AN:

251412

Hom.:

103962

AF XY:

0.916

AC XY:

124480

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.620

Gnomad AMR exome

AF:

0.797

Gnomad ASJ exome

AF:

0.961

Gnomad EAS exome

AF:

0.995

Gnomad SAS exome

AF:

0.965

Gnomad FIN exome

AF:

0.945

Gnomad NFE exome

AF:

0.933

Gnomad OTH exome

AF:

0.926

GnomAD4 exome

AF:

0.924

AC:

1351243

AN:

1461704

Hom.:

627051

Cov.:

AF XY:

0.927

AC XY:

674395

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.606

Gnomad4 AMR exome

AF:

0.801

Gnomad4 ASJ exome

AF:

0.959

Gnomad4 EAS exome

AF:

0.996

Gnomad4 SAS exome

AF:

0.965

Gnomad4 FIN exome

AF:

0.943

Gnomad4 NFE exome

AF:

0.932

Gnomad4 OTH exome

AF:

0.922

GnomAD4 genome

AF:

0.841

AC:

128067

AN:

152198

Hom.:

55355

Cov.:

AF XY:

0.845

AC XY:

62895

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.622

Gnomad4 AMR

AF:

0.823

Gnomad4 ASJ

AF:

0.960

Gnomad4 EAS

AF:

0.990

Gnomad4 SAS

AF:

0.960

Gnomad4 FIN

AF:

0.944

Gnomad4 NFE

AF:

0.934

Gnomad4 OTH

AF:

0.878

Alfa

AF:

0.920

Hom.:

100120

Bravo

AF:

0.825

Asia WGS

AF:

0.952

AC:

3311

AN:

3478

EpiCase

AF:

0.937

EpiControl

AF:

0.936

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neuropathy, hereditary sensory and autonomic, type 1C

Benign:4

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Benign:2

Jul 26, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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