Variant 18-47136426-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001318765.2(HDHD2):c.-294G>A variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000164 in 1,612,470 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

HDHD2
NM_001318765.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.17

Variant links:

Genes affected

HDHD2 (HGNC:25364): (haloacid dehalogenase like hydrolase domain containing 2) Enables enzyme binding activity. Predicted to be involved in dephosphorylation. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

HDHD2 links:

ENSG00000267228 (HGNC:):

ENSG00000267228 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18023568).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDHD2	NM_032124.5 linkuse as main transcript	c.14G>A	p.Arg5His	missense_variant	2/7	ENST00000300605.11	NP_115500.1	Q9H0R4-1V9HW73

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HDHD2	ENST00000300605.11 linkuse as main transcript	c.14G>A	p.Arg5His	missense_variant	2/7	1	NM_032124.5	ENSP00000300605.4	Q9H0R4-1
ENSG00000267228	ENST00000588705.1 linkuse as main transcript	n.*172G>A		non_coding_transcript_exon_variant	5/6	2		ENSP00000465194.1
ENSG00000267228	ENST00000588705.1 linkuse as main transcript	n.*172G>A		3_prime_UTR_variant	5/6	2		ENSP00000465194.1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000401

AC:

AN:

249160

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

134834

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000619

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000175

AC:

255

AN:

1460278

Hom.:

Cov.:

AF XY:

0.000167

AC XY:

121

AN XY:

726576

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000220

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000256

Hom.:

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Ambry Genetics

Nov 10, 2024

The c.14G>A (p.R5H) alteration is located in exon 2 (coding exon 1) of the HDHD2 gene. This alteration results from a G to A substitution at nucleotide position 14, causing the arginine (R) at amino acid position 5 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

T;.;T;.;.;T;T

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

T;T;T;.;T;T;T

M_CAP

Benign

0.0077

MetaRNN

Benign

0.18

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.;.;.;.;.;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.6

N;.;.;.;.;.;.

REVEL

Benign

0.070

Sift

Uncertain

0.013

D;.;.;.;.;.;.

Sift4G

Benign

0.072

T;.;T;.;T;.;T

Polyphen

0.23

B;.;.;.;.;.;.

Vest4

0.31

MVP

0.47

MPC

0.26

ClinPred

0.081

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.25

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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