1-119384785-C-T

Variant names:

• chr1-119384785-C-T
• rs142375074
• NM_016527.4:c.293C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016527.4(HAO2):​c.293C>T​(p.Ala98Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,613,596 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 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. A98E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: HAO2 NM_016527.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30
• Publications: 8 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016527.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAO2	NM_016527.4	MANE Select	c.293C>T	p.Ala98Val	missense	Exon 4 of 8	NP_057611.1	Q9NYQ3-1
	HAO2	NM_001005783.3		c.332C>T	p.Ala111Val	missense	Exon 5 of 9	NP_001005783.2	Q9NYQ3-2
	HAO2	NM_001377472.1		c.332C>T	p.Ala111Val	missense	Exon 5 of 8	NP_001364401.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAO2	ENST00000325945.4	TSL:1 MANE Select	c.293C>T	p.Ala98Val	missense	Exon 4 of 8	ENSP00000316339.3	Q9NYQ3-1
	HAO2	ENST00000361035.8	TSL:1	c.332C>T	p.Ala111Val	missense	Exon 5 of 9	ENSP00000354314.4	Q9NYQ3-2
	HAO2	ENST00000622548.4	TSL:1	c.293C>T	p.Ala98Val	missense	Exon 5 of 9	ENSP00000483507.1	Q9NYQ3-1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152176 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000520 AC: 13 AN: 250118 AF XY: 0.0000370

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000798

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000287 AC: 42 AN: 1461420 Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17 AN XY: 727002

African (AFR) AF: 0.0000299 AC: 1 AN: 33468

American (AMR) AF: 0.0000224 AC: 1 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39630

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000288 AC: 32 AN: 1111764

Other (OTH) AF: 0.0000828 AC: 5 AN: 60366

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152176 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74338

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000395 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000577 AC: 7

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Benign	0.019
Eigen_PC	Benign	-0.040
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.3
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.13
Sift	Benign	0.039	D
Sift4G	Benign	0.070	T
Polyphen		0.90	P
Vest4		0.47
MutPred		0.60		Loss of helix (P = 0.0033)
MVP		0.44
MPC		0.076
ClinPred		0.25	T
GERP RS		2.3
Varity_R		0.22
gMVP		0.69
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs142375074; hg19: chr1-119927408; COSMIC: COSV58038729;