Genetic Variant HACD2:p.Gly18Ser (chr3-123584976-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198402.5(HACD2):c.52G>A(p.Gly18Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G18C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HACD2
NM_198402.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.196

Publications

0 publications found

Variant links:

Genes affected

HACD2 (HGNC:9640): (3-hydroxyacyl-CoA dehydratase 2) The protein encoded by this gene can catalyze the third step (dehydration) in the conversion of long chain fatty acids to very long chain fatty acids. The encoded protein localizes to the endoplasmic reticulum membrane. [provided by RefSeq, Jul 2016]

HACD2 links:

MYLK-AS1 (HGNC:42440): (MYLK antisense RNA 1)

MYLK-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051594228).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HACD2	NM_198402.5 link	c.52G>A	p.Gly18Ser	missense_variant	Exon 1 of 7	ENST00000383657.10	NP_940684.1	Q6Y1H2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HACD2	ENST00000383657.10 link	c.52G>A	p.Gly18Ser	missense_variant	Exon 1 of 7	1	NM_198402.5	ENSP00000373153.5		Q6Y1H2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

118372

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

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:

AN:

1373110

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

676992

African (AFR)

AF:

0.00

AC:

AN:

28258

American (AMR)

AF:

0.00

AC:

AN:

33270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24234

East Asian (EAS)

AF:

0.00

AC:

AN:

31790

South Asian (SAS)

AF:

0.00

AC:

AN:

77056

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4928

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1069178

Other (OTH)

AF:

0.00

AC:

AN:

56976

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.0083

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.50

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

PhyloP100

0.20

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

0.14

REVEL

Benign

0.031

Sift

Benign

1.0

Sift4G

Benign

0.37

Polyphen

0.0

Vest4

0.16

MutPred

0.29

Gain of glycosylation at G18 (P = 8e-04);

MVP

0.068

MPC

0.66

ClinPred

0.083

GERP RS

1.0

PromoterAI

0.067

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.056

gMVP

0.48

Mutation Taster

=86/14

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over