chr1-119384827-G-A

Position:

• chr1-119384827-G-A

Variant summary

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

The NM_016527.4(HAO2):​c.335G>A​(p.Ser112Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HAO2 NM_016527.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.42

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 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	c.335G>A	p.Ser112Asn	missense_variant	4/8	ENST00000325945.4	NP_057611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAO2	ENST00000325945.4	c.335G>A	p.Ser112Asn	missense_variant	4/8	1	NM_016527.4	ENSP00000316339.3
HAO2	ENST00000361035.8	c.374G>A	p.Ser125Asn	missense_variant	5/9	1		ENSP00000354314.4
HAO2	ENST00000622548.4	c.335G>A	p.Ser112Asn	missense_variant	5/9	1		ENSP00000483507.1
HAO2	ENST00000457318.5	c.284-24G>A		intron_variant		3		ENSP00000393955.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.335G>A (p.S112N) alteration is located in exon 5 (coding exon 3) of the HAO2 gene. This alteration results from a G to A substitution at nucleotide position 335, causing the serine (S) at amino acid position 112 to be replaced by an asparagine (N). 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	0.15
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.36	T;.;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.71	T;T;.
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Pathogenic	3.2	M;.;M
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.3	.;N;N
REVEL	Benign	0.16
Sift	Uncertain	0.0090	.;D;D
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		0.12	B;.;B
Vest4		0.22
MutPred		0.71		Gain of helix (P = 0.0199);.;Gain of helix (P = 0.0199);
MVP		0.41
MPC		0.073
ClinPred		0.85	D
GERP RS		1.3
Varity_R		0.24
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.29		Position offset: 24

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-119927450;