Variant 18-47134683-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001318765.2(HDHD2):c.-148C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,964 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HDHD2
NM_001318765.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0490

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04224834).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDHD2	NM_032124.5 linkuse as main transcript	c.123C>G	p.Ile41Met	missense_variant	3/7	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.123C>G	p.Ile41Met	missense_variant	3/7	1	NM_032124.5	ENSP00000300605.4	Q9H0R4-1
ENSG00000267228	ENST00000588705.1 linkuse as main transcript	n.*281C>G		non_coding_transcript_exon_variant	6/6	2		ENSP00000465194.1
ENSG00000267228	ENST00000588705.1 linkuse as main transcript	n.*281C>G		3_prime_UTR_variant	6/6	2		ENSP00000465194.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461774

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 22, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.36

DANN

Benign

0.37

DEOGEN2

Benign

0.011

T;.;.;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.74

T;T;.;T;T

M_CAP

Benign

0.0037

MetaRNN

Benign

0.042

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

N;.;.;.;.

PrimateAI

Benign

0.25

PROVEAN

Benign

0.90

N;.;.;.;.

REVEL

Benign

0.013

Sift

Benign

0.23

T;.;.;.;.

Sift4G

Benign

0.14

T;.;.;T;.

Polyphen

0.0

B;.;.;.;.

Vest4

0.051

MVP

0.18

MPC

0.21

ClinPred

0.030

GERP RS

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.30

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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