Variant 1-119382926-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016527.4(HAO2):c.143G>A(p.Arg48His) variant causes a missense change. The variant allele was found at a frequency of 0.0000744 in 1,613,576 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000073 ( 1 hom. )

Consequence

HAO2
NM_016527.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.40

Variant links:

Genes affected

HAO2 (HGNC:4810): (hydroxyacid oxidase 2) This gene is one of three related genes that have 2-hydroxyacid oxidase activity. The encoded protein localizes to the peroxisome has the highest activity toward the substrate 2-hydroxypalmitate. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

HAO2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3604446).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAO2	NM_016527.4 linkuse as main transcript	c.143G>A	p.Arg48His	missense_variant	3/8	ENST00000325945.4	NP_057611.1	Q9NYQ3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HAO2	ENST00000325945.4 linkuse as main transcript	c.143G>A	p.Arg48His	missense_variant	3/8	1	NM_016527.4	ENSP00000316339.3	Q9NYQ3-1
HAO2	ENST00000361035.8 linkuse as main transcript	c.182G>A	p.Arg61His	missense_variant	4/9	1		ENSP00000354314.4	Q9NYQ3-2
HAO2	ENST00000622548.4 linkuse as main transcript	c.143G>A	p.Arg48His	missense_variant	4/9	1		ENSP00000483507.1	Q9NYQ3-1
HAO2	ENST00000457318.5 linkuse as main transcript	c.143G>A	p.Arg48His	missense_variant	3/5	3		ENSP00000393955.1	Q5QP02

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000479

AC:

AN:

250370

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135278

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000443

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000725

AC:

106

AN:

1461276

Hom.:

Cov.:

AF XY:

0.0000770

AC XY:

AN XY:

726930

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000454

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000648

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000919

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000177

Hom.:

Bravo

AF:

0.0000453

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000577

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

Jun 13, 2023

The c.143G>A (p.R48H) alteration is located in exon 4 (coding exon 2) of the HAO2 gene. This alteration results from a G to A substitution at nucleotide position 143, causing the arginine (R) at amino acid position 48 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

0.19

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.061

T;T;.;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.99

D;D;D;.

M_CAP

Benign

0.026

MetaRNN

Benign

0.36

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.7

.;M;.;M

PrimateAI

Uncertain

0.48

PROVEAN

Uncertain

-2.6

D;.;D;D

REVEL

Benign

0.19

Sift

Uncertain

0.024

D;.;D;D

Sift4G

Uncertain

0.050

T;T;T;T

Polyphen

0.99

.;D;.;D

Vest4

0.79, 0.79, 0.78

MVP

0.58

MPC

0.22

ClinPred

0.60

GERP RS

3.8

Varity_R

0.61

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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