Variant X-57448667-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_174912.4(FAAH2):c.1372G>T(p.Ala458Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000271 in 1,209,408 control chromosomes in the GnomAD database, including 2 homozygotes. There are 101 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., 5 hem., cov: 23)

Exomes 𝑓: 0.00028 ( 2 hom. 96 hem. )

Consequence

FAAH2
NM_174912.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 5.50

Variant links:

Genes affected

FAAH2 (HGNC:26440): (fatty acid amide hydrolase 2) This gene encodes a fatty acid amide hydrolase that shares a conserved protein motif with the amidase signature family of enzymes. The encoded enzyme is able to catalyze the hydrolysis of a broad range of bioactive lipids, including those from the three main classes of fatty acid amides; N-acylethanolamines, fatty acid primary amides and N-acyl amino acids. This enzyme has a preference for monounsaturated acyl chains as a substrate. Alternate splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2017]

FAAH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09746036).

BS2

High Hemizygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAAH2	NM_174912.4 linkuse as main transcript	c.1372G>T	p.Ala458Ser	missense_variant	10/11	ENST00000374900.5	NP_777572.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
FAAH2	ENST00000374900.5 linkuse as main transcript	c.1372G>T	p.Ala458Ser	missense_variant	10/11	1	NM_174912.4	ENSP00000364035	P1
FAAH2	ENST00000491179.1 linkuse as main transcript	n.51-15G>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		1
FAAH2	ENST00000465623.1 linkuse as main transcript	n.296G>T		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes

AF:

0.000143

AC:

AN:

111654

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

33848

show subpopulations

Gnomad AFR

AF:

0.0000326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000381

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:

0.000207

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000509

AC:

AN:

182549

Hom.:

AF XY:

0.000432

AC XY:

AN XY:

67083

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000724

Gnomad SAS exome

AF:

0.000106

Gnomad FIN exome

AF:

0.000313

Gnomad NFE exome

AF:

0.000981

Gnomad OTH exome

AF:

0.000444

GnomAD4 exome

AF:

0.000284

AC:

312

AN:

1097697

Hom.:

Cov.:

AF XY:

0.000264

AC XY:

AN XY:

363123

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000171

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000994

Gnomad4 SAS exome

AF:

0.000167

Gnomad4 FIN exome

AF:

0.000568

Gnomad4 NFE exome

AF:

0.000297

Gnomad4 OTH exome

AF:

0.000456

GnomAD4 genome

AF:

0.000143

AC:

AN:

111711

Hom.:

Cov.:

AF XY:

0.000147

AC XY:

AN XY:

33915

show subpopulations

Gnomad4 AFR

AF:

0.0000325

Gnomad4 AMR

AF:

0.000380

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000207

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.000174

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000873

AC:

106

EpiCase

AF:

0.000219

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Mar 01, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.89

M_CAP

Pathogenic

0.50

MetaRNN

Benign

0.097

MetaSVM

Uncertain

-0.17

MutationAssessor

Pathogenic

3.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.51

Sift

Benign

0.041

Sift4G

Uncertain

0.037

Polyphen

1.0

Vest4

0.47

MVP

0.75

MPC

0.0017

ClinPred

0.21

GERP RS

2.5

Varity_R

0.54

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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