rs1555959573

Variant names:

• chrX-57292569-TGTCAAGTACAG-T
• rs1555959573
• ENST00000374900.5:c.231_241delGTCAAGTACAG

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM4 PP5_Moderate

The NM_174912.4(FAAH2):​c.267_275+2delCAAGTACAGGT​(p.Lys90_Arg92del) variant causes a splice donor, disruptive inframe deletion, splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: FAAH2 NM_174912.4 splice_donor, disruptive_inframe_deletion, splice_region, intron
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 3.28
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_174912.4.
• PP5: Variant X-57292569-TGTCAAGTACAG-T is Pathogenic according to our data. Variant chrX-57292569-TGTCAAGTACAG-T is described in ClinVar as Pathogenic. ClinVar VariationId is 522688.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174912.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAAH2	NM_174912.4	MANE Select	c.267_275+2delCAAGTACAGGT	p.Lys90_Arg92del	splice_donor disruptive_inframe_deletion splice_region intron	Exon 2 of 11	NP_777572.2	Q6GMR7
	FAAH2	NM_001353840.1		c.267_275+2delCAAGTACAGGT	p.Lys90_Arg92del	splice_donor disruptive_inframe_deletion splice_region intron	Exon 2 of 10	NP_001340769.1
	FAAH2	NM_001353841.1		c.267_275+2delCAAGTACAGGT	p.Lys90_Arg92del	splice_donor disruptive_inframe_deletion splice_region intron	Exon 2 of 10	NP_001340770.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAAH2	ENST00000374900.5	TSL:1 MANE Select	c.231_241delGTCAAGTACAG	p.Arg77fs	frameshift	Exon 2 of 11	ENSP00000364035.4	Q6GMR7
	FAAH2	ENST00000886040.1		c.231_241delGTCAAGTACAG	p.Arg77fs	frameshift	Exon 2 of 12	ENSP00000556099.1
	FAAH2	ENST00000972153.1		c.231_241delGTCAAGTACAG	p.Arg77fs	frameshift	Exon 2 of 11	ENSP00000642212.1

Frequencies

GnomAD3 genomes Cov.: 22

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.3
Mutation Taster		=40/160	disease causing (ClinVar)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1555959573; hg19: chrX-57319002;