16-74716507-G-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_024306.5(FA2H):ā€‹c.879C>Gā€‹(p.Pro293Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 151,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P293P) has been classified as Benign.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 29)
Exomes š‘“: 0.0000075 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

FA2H
NM_024306.5 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.58
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP7
Synonymous conserved (PhyloP=-2.58 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FA2HNM_024306.5 linkuse as main transcriptc.879C>G p.Pro293Pro synonymous_variant 6/7 ENST00000219368.8 NP_077282.3 Q7L5A8-1
FA2HXM_011523319.3 linkuse as main transcriptc.639C>G p.Pro213Pro synonymous_variant 6/7 XP_011521621.1
FA2HXM_011523317.4 linkuse as main transcriptc.*1743C>G 3_prime_UTR_variant 6/6 XP_011521619.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FA2HENST00000219368.8 linkuse as main transcriptc.879C>G p.Pro293Pro synonymous_variant 6/71 NM_024306.5 ENSP00000219368.3 Q7L5A8-1
FA2HENST00000562145.1 linkuse as main transcriptn.600C>G non_coding_transcript_exon_variant 1/21
FA2HENST00000567683.5 linkuse as main transcriptn.*158C>G non_coding_transcript_exon_variant 4/52 ENSP00000455126.1 H3BP32
FA2HENST00000567683.5 linkuse as main transcriptn.*158C>G 3_prime_UTR_variant 4/52 ENSP00000455126.1 H3BP32

Frequencies

GnomAD3 genomes
AF:
0.00000660
AC:
1
AN:
151628
Hom.:
0
Cov.:
29
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000753
AC:
11
AN:
1461304
Hom.:
0
Cov.:
64
AF XY:
0.00000550
AC XY:
4
AN XY:
726954
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:
0.00000989
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000660
AC:
1
AN:
151628
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
74010
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:
0.0000147
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
0.020
DANN
Benign
0.54

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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.

Other links and lift over

dbSNP: rs2301865; hg19: chr16-74750405; API