Variant 6-10983801-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017770.4(ELOVL2):c.871A>G(p.Met291Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,610,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

ELOVL2
NM_017770.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.435

Variant links:

Genes affected

ELOVL2 (HGNC:14416): (ELOVL fatty acid elongase 2) Enables fatty acid elongase activity. Involved in fatty acid elongation, polyunsaturated fatty acid and very long-chain fatty acid biosynthetic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ELOVL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055158198).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ELOVL2	NM_017770.4 linkuse as main transcript	c.871A>G	p.Met291Val	missense_variant	8/8	ENST00000354666.4
ELOVL2	XM_011514716.4 linkuse as main transcript	c.961A>G	p.Met321Val	missense_variant	8/8
ELOVL2	XM_011514717.4 linkuse as main transcript	c.874A>G	p.Met292Val	missense_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELOVL2	ENST00000354666.4 linkuse as main transcript	c.871A>G	p.Met291Val	missense_variant	8/8	1	NM_017770.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1458290

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

725386

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 18, 2023

The c.871A>G (p.M291V) alteration is located in exon 8 (coding exon 8) of the ELOVL2 gene. This alteration results from a A to G substitution at nucleotide position 871, causing the methionine (M) at amino acid position 291 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.79

Cadd

Benign

0.95

Dann

Benign

0.69

DEOGEN2

Benign

0.10

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.50

M_CAP

Benign

0.0060

MetaRNN

Benign

0.055

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

0.050

REVEL

Benign

0.017

Sift

Benign

0.32

Sift4G

Benign

0.36

Polyphen

0.0

Vest4

0.024

MVP

0.067

MPC

0.13

ClinPred

0.081

GERP RS

1.6

Varity_R

0.050

gMVP

0.40

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