chr1-119381178-C-G

Variant names:

• chr1-119381178-C-G
• rs775550007
• NM_016527.4:c.93C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_016527.4(HAO2):​c.93C>G​(p.Asp31Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000453 in 1,610,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000048 (0 hom.)
• Consequence: HAO2 NM_016527.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.44

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

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=0.0785152).
• BP6: Variant 1-119381178-C-G is Benign according to our data. Variant chr1-119381178-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3856736.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAO2	NM_016527.4	c.93C>G	p.Asp31Glu	missense_variant	Exon 2 of 8	ENST00000325945.4	NP_057611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAO2	ENST00000325945.4	c.93C>G	p.Asp31Glu	missense_variant	Exon 2 of 8	1	NM_016527.4	ENSP00000316339.3
HAO2	ENST00000361035.8	c.132C>G	p.Asp44Glu	missense_variant	Exon 3 of 9	1		ENSP00000354314.4
HAO2	ENST00000622548.4	c.93C>G	p.Asp31Glu	missense_variant	Exon 3 of 9	1		ENSP00000483507.1
HAO2	ENST00000457318.5	c.93C>G	p.Asp31Glu	missense_variant	Exon 2 of 5	3		ENSP00000393955.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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

GnomAD3 exomes AF: 0.0000239 AC: 6 AN: 251210 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135762

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: 0.0000352

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000480 AC: 70 AN: 1457832 Hom.: 0 Cov.: 29 AF XY: 0.0000455 AC XY: 33 AN XY: 725570

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: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000550

Gnomad4 OTH exome AF: 0.000116

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152184 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74324

Gnomad4 AFR AF: 0.0000241

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

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 27, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	0.15
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.0020
DANN	Benign	0.67
DEOGEN2	Benign	0.019	T;T;.;T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.72	T;T;T;.
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.079	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.66	.;N;.;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.2	N;.;N;N
REVEL	Benign	0.055
Sift	Benign	0.42	T;.;T;T
Sift4G	Benign	0.72	T;T;T;T
Polyphen		0.0	.;B;.;B
Vest4		0.21, 0.22, 0.15
MutPred		0.61		Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);.;Loss of helix (P = 0.1706);
MVP		0.34
MPC		0.024
ClinPred		0.048	T
GERP RS		-10
Varity_R		0.031
gMVP		0.46

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

Other links and lift over

dbSNP: rs775550007; hg19: chr1-119923801;