chr16-74774639-G-A

Variant names:

• chr16-74774639-G-A
• rs794729215
• NM_024306.5:c.117C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024306.5(FA2H):​c.117C>T​(p.Phe39Phe) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FA2H NM_024306.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.67
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia 35

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FA2H	NM_024306.5	c.117C>T	p.Phe39Phe	synonymous_variant	Exon 1 of 7	ENST00000219368.8	NP_077282.3
FA2H	XM_011523317.4	c.117C>T	p.Phe39Phe	synonymous_variant	Exon 1 of 6		XP_011521619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FA2H	ENST00000219368.8	c.117C>T	p.Phe39Phe	synonymous_variant	Exon 1 of 7	1	NM_024306.5	ENSP00000219368.3
FA2H	ENST00000567683.5	n.117C>T		non_coding_transcript_exon_variant	Exon 1 of 5	2		ENSP00000455126.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000107 AC: 1 AN: 93850 AF XY: 0.0000188

Gnomad AFR exome AF: 0.000591

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1338826 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 660618

African (AFR) AF: 0.00 AC: 0 AN: 27594

American (AMR) AF: 0.00 AC: 0 AN: 30194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23676

East Asian (EAS) AF: 0.00 AC: 0 AN: 30040

South Asian (SAS) AF: 0.00 AC: 0 AN: 73836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34082

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4186

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1059432

Other (OTH) AF: 0.00 AC: 0 AN: 55786

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	15
DANN	Uncertain	0.98
PhyloP100		4.7
PromoterAI		0.021	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs794729215; hg19: chr16-74808537;