Variant 1-119383030-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016527.4(HAO2):c.247C>T(p.Leu83Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,840 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HAO2
NM_016527.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.403

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAO2	NM_016527.4 linkuse as main transcript	c.247C>T	p.Leu83Phe	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.247C>T	p.Leu83Phe	missense_variant	3/8	1	NM_016527.4	ENSP00000316339.3	Q9NYQ3-1
HAO2	ENST00000361035.8 linkuse as main transcript	c.286C>T	p.Leu96Phe	missense_variant	4/9	1		ENSP00000354314.4	Q9NYQ3-2
HAO2	ENST00000622548.4 linkuse as main transcript	c.247C>T	p.Leu83Phe	missense_variant	4/9	1		ENSP00000483507.1	Q9NYQ3-1
HAO2	ENST00000457318.5 linkuse as main transcript	c.247C>T	p.Leu83Phe	missense_variant	3/5	3		ENSP00000393955.1	Q5QP02

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249714

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134944

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460840

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726686

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Dec 18, 2023

The c.247C>T (p.L83F) alteration is located in exon 4 (coding exon 2) of the HAO2 gene. This alteration results from a C to T substitution at nucleotide position 247, causing the leucine (L) at amino acid position 83 to be replaced by a phenylalanine (F). 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

0.21

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.054

T;T;.;T

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.60

LIST_S2

Uncertain

0.93

D;D;D;.

M_CAP

Benign

0.0090

MetaRNN

Uncertain

0.45

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

.;M;.;M

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.8

D;.;D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0030

D;.;D;D

Sift4G

Benign

0.14

T;T;T;T

Polyphen

0.32

.;B;.;B

Vest4

0.39, 0.42

MutPred

0.68

Loss of solvent accessibility (P = 0.0769);Loss of solvent accessibility (P = 0.0769);.;Loss of solvent accessibility (P = 0.0769);

MVP

0.33

MPC

0.030

ClinPred

0.52

GERP RS

1.3

Varity_R

0.17

gMVP

0.81

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