7-90225546-A-G

Position:

• chr7-90225546-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001244944.2(STEAP2):​c.464A>G​(p.Gln155Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STEAP2 NM_001244944.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.31

Genes affected

STEAP2 (HGNC:17885): (STEAP2 metalloreductase) This gene is a member of the STEAP family and encodes a multi-pass membrane protein that localizes to the Golgi complex, the plasma membrane, and the vesicular tubular structures in the cytosol. A highly similar protein in mouse has both ferrireductase and cupric reductase activity, and stimulates the cellular uptake of both iron and copper in vitro. Increased transcriptional expression of the human gene is associated with prostate cancer progression. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

STEAP2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.924

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STEAP2	NM_001244944.2	c.464A>G	p.Gln155Arg	missense_variant	3/6	ENST00000394621.7	NP_001231873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STEAP2	ENST00000394621.7	c.464A>G	p.Gln155Arg	missense_variant	3/6	1	NM_001244944.2	ENSP00000378119.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

Nov 21, 2024

The c.464A>G (p.Q155R) alteration is located in exon 2 (coding exon 1) of the STEAP2 gene. This alteration results from a A to G substitution at nucleotide position 464, causing the glutamine (Q) at amino acid position 155 to be replaced by an arginine (R). 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	Uncertain	0.36
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;T;T;.;T;.;T;.
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;.;D;.;.;D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.92	D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	.;M;M;M;M;M;.;M
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.7	D;D;D;D;D;D;D;D
REVEL	Uncertain	0.63
Sift	Uncertain	0.0010	D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.028	D;D;D;D;D;D;D;D
Polyphen		1.0	.;D;D;.;D;.;D;.
Vest4		0.82, 0.81, 0.81, 0.83, 0.82, 0.82, 0.81
MutPred		0.79		Gain of MoRF binding (P = 0.0244);Gain of MoRF binding (P = 0.0244);Gain of MoRF binding (P = 0.0244);Gain of MoRF binding (P = 0.0244);Gain of MoRF binding (P = 0.0244);Gain of MoRF binding (P = 0.0244);Gain of MoRF binding (P = 0.0244);Gain of MoRF binding (P = 0.0244);
MVP		0.57
MPC		0.27
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.69
gMVP		0.91

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-89854860;