Variant rs794729214 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_024306.5(FA2H):c.160_169delGCGGGCCAGG(p.Ala54fs) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000217 in 1,382,154 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

FA2H
NM_024306.5 frameshift

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 6.89

Variant links:

Genes affected

FA2H (HGNC:21197): (fatty acid 2-hydroxylase) This gene encodes a protein that catalyzes the synthesis of 2-hydroxysphingolipids, a subset of sphingolipids that contain 2-hydroxy fatty acids. Sphingolipids play roles in many cellular processes and their structural diversity arises from modification of the hydrophobic ceramide moiety, such as by 2-hydroxylation of the N-acyl chain, and the existence of many different head groups. Mutations in this gene have been associated with leukodystrophy dysmyelinating with spastic paraparesis with or without dystonia.[provided by RefSeq, Mar 2010]

FA2H links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 16-74774586-TCCTGGCCCGC-T is Pathogenic according to our data. Variant chr16-74774586-TCCTGGCCCGC-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 803272.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FA2H	NM_024306.5 link	c.160_169delGCGGGCCAGG	p.Ala54fs	frameshift_variant	1/7	ENST00000219368.8	NP_077282.3	Q7L5A8-1
FA2H	XM_011523317.4 link	c.160_169delGCGGGCCAGG	p.Ala54fs	frameshift_variant	1/6		XP_011521619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FA2H	ENST00000219368.8 link	c.160_169delGCGGGCCAGG	p.Ala54fs	frameshift_variant	1/7	1	NM_024306.5	ENSP00000219368.3		Q7L5A8-1
FA2H	ENST00000567683.5 link	n.160_169delGCGGGCCAGG		non_coding_transcript_exon_variant	1/5	2		ENSP00000455126.1		H3BP32

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000217

AC:

AN:

1382154

Hom.:

AF XY:

0.00000292

AC XY:

AN XY:

683846

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:

0.00000277

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 35

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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