rs367686182

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting

The NM_024306.5(FA2H):​c.*6C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000413 in 1,548,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

FA2H
NM_024306.5 3_prime_UTR

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0320
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).
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00025 (38/152204) while in subpopulation AFR AF= 0.000893 (37/41450). AF 95% confidence interval is 0.000666. There are 0 homozygotes in gnomad4. There are 22 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FA2HNM_024306.5 linkc.*6C>G 3_prime_UTR_variant Exon 7 of 7 ENST00000219368.8 NP_077282.3 Q7L5A8-1
FA2HXM_011523319.3 linkc.*6C>G 3_prime_UTR_variant Exon 7 of 7 XP_011521621.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FA2HENST00000219368 linkc.*6C>G 3_prime_UTR_variant Exon 7 of 7 1 NM_024306.5 ENSP00000219368.3 Q7L5A8-1
FA2HENST00000562145.1 linkn.846C>G non_coding_transcript_exon_variant Exon 2 of 2 1
FA2HENST00000567683.5 linkn.*404C>G non_coding_transcript_exon_variant Exon 5 of 5 2 ENSP00000455126.1 H3BP32
FA2HENST00000567683.5 linkn.*404C>G 3_prime_UTR_variant Exon 5 of 5 2 ENSP00000455126.1 H3BP32

Frequencies

GnomAD3 genomes
AF:
0.000250
AC:
38
AN:
152204
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000893
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:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000607
AC:
10
AN:
164640
Hom.:
0
AF XY:
0.0000690
AC XY:
6
AN XY:
86970
show subpopulations
Gnomad AFR exome
AF:
0.00106
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000186
AC:
26
AN:
1396750
Hom.:
0
Cov.:
29
AF XY:
0.0000145
AC XY:
10
AN XY:
690162
show subpopulations
Gnomad4 AFR exome
AF:
0.000662
Gnomad4 AMR exome
AF:
0.0000275
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:
0.00000279
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
AF:
0.000250
AC:
38
AN:
152204
Hom.:
0
Cov.:
32
AF XY:
0.000296
AC XY:
22
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.000893
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:
0.00
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000847
Hom.:
0
Bravo
AF:
0.000325

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoJul 17, 2015- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
7.7
DANN
Benign
0.75

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.

Other links and lift over

dbSNP: rs367686182; hg19: chr16-74748082; API