chrX-57310619-A-G

Position:

• chrX-57310619-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_174912.4(FAAH2):​c.302A>G​(p.His101Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: FAAH2 NM_174912.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.191

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 (HGNC:):

ACMG classification

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=0.06156954).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAAH2	NM_174912.4	c.302A>G	p.His101Arg	missense_variant	3/11	ENST00000374900.5	NP_777572.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAAH2	ENST00000374900.5	c.302A>G	p.His101Arg	missense_variant	3/11	1	NM_174912.4	ENSP00000364035.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 31, 2024

The c.302A>G (p.H101R) alteration is located in exon 3 (coding exon 3) of the FAAH2 gene. This alteration results from a A to G substitution at nucleotide position 302, causing the histidine (H) at amino acid position 101 to be replaced by an arginine (R). 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	0.057
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.3
DANN	Benign	0.40
DEOGEN2	Benign	0.013	T
FATHMM_MKL	Benign	0.0099	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.0	N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.10
Sift	Benign	0.92	T
Sift4G	Benign	0.64	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.42		Gain of MoRF binding (P = 0.069);
MVP		0.79
MPC		0.00075
ClinPred		0.037	T
GERP RS		0.53
Varity_R		0.10
gMVP		0.21

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: rs2052666158; hg19: chrX-57337052;