rs367686182
Variant names:
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
NM_024306.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0320
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]
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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
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FA2H | ENST00000219368 | c.*6C>G | 3_prime_UTR_variant | Exon 7 of 7 | 1 | NM_024306.5 | ENSP00000219368.3 | |||
FA2H | ENST00000562145.1 | n.846C>G | non_coding_transcript_exon_variant | Exon 2 of 2 | 1 | |||||
FA2H | ENST00000567683.5 | n.*404C>G | non_coding_transcript_exon_variant | Exon 5 of 5 | 2 | ENSP00000455126.1 | ||||
FA2H | ENST00000567683.5 | n.*404C>G | 3_prime_UTR_variant | Exon 5 of 5 | 2 | ENSP00000455126.1 |
Frequencies
GnomAD3 genomes AF: 0.000250 AC: 38AN: 152204Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000607 AC: 10AN: 164640Hom.: 0 AF XY: 0.0000690 AC XY: 6AN XY: 86970
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GnomAD4 exome AF: 0.0000186 AC: 26AN: 1396750Hom.: 0 Cov.: 29 AF XY: 0.0000145 AC XY: 10AN XY: 690162
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GnomAD4 genome AF: 0.000250 AC: 38AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 22AN XY: 74358
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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 submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 17, 2015 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at