Variant chr16-74713907-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024306.5(FA2H):c.*283G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0313 in 432,770 control chromosomes in the GnomAD database, including 1,071 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 842 hom., cov: 33)

Exomes 𝑓: 0.014 ( 229 hom. )

Consequence

FA2H
NM_024306.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.316

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]

FA2H links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 16-74713907-C-G is Benign according to our data. Variant chr16-74713907-C-G is described in ClinVar as [Benign]. Clinvar id is 320484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FA2H	NM_024306.5 linkuse as main transcript	c.*283G>C		3_prime_UTR_variant	7/7	ENST00000219368.8
FA2H	XM_011523319.3 linkuse as main transcript	c.*283G>C		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FA2H	ENST00000219368.8 linkuse as main transcript	c.*283G>C	3_prime_UTR_variant	7/7	1	NM_024306.5	P1	Q7L5A8-1
FA2H	ENST00000562145.1 linkuse as main transcript	n.1123G>C	non_coding_transcript_exon_variant	2/2	1
FA2H	ENST00000567683.5 linkuse as main transcript	c.*681G>C	3_prime_UTR_variant, NMD_transcript_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.0626

AC:

9523

AN:

152098

Hom.:

842

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0214

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.0143

Gnomad FIN

AF:

0.0167

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00513

Gnomad OTH

AF:

0.0407

GnomAD4 exome

AF:

0.0142

AC:

3996

AN:

280554

Hom.:

229

Cov.:

AF XY:

0.0133

AC XY:

1918

AN XY:

144366

show subpopulations

Gnomad4 AFR exome

AF:

0.205

Gnomad4 AMR exome

AF:

0.0150

Gnomad4 ASJ exome

AF:

0.00352

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0133

Gnomad4 FIN exome

AF:

0.0163

Gnomad4 NFE exome

AF:

0.00499

Gnomad4 OTH exome

AF:

0.0202

GnomAD4 genome

AF:

0.0626

AC:

9532

AN:

152216

Hom.:

842

Cov.:

AF XY:

0.0608

AC XY:

4529

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.205

Gnomad4 AMR

AF:

0.0214

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.000388

Gnomad4 SAS

AF:

0.0137

Gnomad4 FIN

AF:

0.0167

Gnomad4 NFE

AF:

0.00513

Gnomad4 OTH

AF:

0.0402

Alfa

AF:

0.00312

Hom.:

Bravo

AF:

0.0701

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 17, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hereditary spastic paraplegia 35

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.3

DANN

Benign

0.61

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over