rs11554620

Variant names:

• chr16-74716453-A-C
• NM_024306.5:c.933T>G

Your query was ambiguous. Multiple possible variants found:

• chr16-74716453-A-C
• chr16-74716453-A-G
• chr16-74716453-A-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_024306.5(FA2H):​c.933T>G​(p.Tyr311*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. Y311Y) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FA2H NM_024306.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.166 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FA2H	NM_024306.5	c.933T>G	p.Tyr311*	stop_gained	Exon 6 of 7	ENST00000219368.8	NP_077282.3
FA2H	XM_011523319.3	c.693T>G	p.Tyr231*	stop_gained	Exon 6 of 7		XP_011521621.1
FA2H	XM_011523317.4	c.*1797T>G		3_prime_UTR_variant	Exon 6 of 6		XP_011521619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FA2H	ENST00000219368.8	c.933T>G	p.Tyr311*	stop_gained	Exon 6 of 7	1	NM_024306.5	ENSP00000219368.3
FA2H	ENST00000562145.1	n.654T>G		non_coding_transcript_exon_variant	Exon 1 of 2	1
FA2H	ENST00000567683.5	n.*212T>G		non_coding_transcript_exon_variant	Exon 4 of 5	2		ENSP00000455126.1
FA2H	ENST00000567683.5	n.*212T>G		3_prime_UTR_variant	Exon 4 of 5	2		ENSP00000455126.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.45
CADD	Pathogenic	37
DANN	Uncertain	0.99
Eigen	Benign	-0.089
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.57	D
Vest4		0.83
GERP RS		-2.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-74750351;