7-90227301-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001244944.2(STEAP2):c.823C>A(p.Leu275Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: STEAP2 NM_001244944.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.95

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22907937).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STEAP2	NM_001244944.2	c.823C>A	p.Leu275Ile	missense_variant	4/6	ENST00000394621.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STEAP2	ENST00000394621.7	c.823C>A	p.Leu275Ile	missense_variant	4/6	1	NM_001244944.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

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

Dec 01, 2022

The c.823C>A (p.L275I) alteration is located in exon 3 (coding exon 2) of the STEAP2 gene. This alteration results from a C to A substitution at nucleotide position 823, causing the leucine (L) at amino acid position 275 to be replaced by an isoleucine (I). 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	0.083
BayesDel_addAF	Uncertain	0.069	T
BayesDel_noAF	Benign	-0.14
Cadd	Benign	21
Dann	Benign	0.96
DEOGEN2	Benign	0.064	T;T;.;T;.;T;.
Eigen	Benign	-0.038
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.23	T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Benign	-0.51	N;N;N;N;N;.;N
MutationTaster	Benign	0.96	D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.67	N;N;N;N;N;N;N
REVEL	Uncertain	0.41
Sift	Benign	0.49	T;T;T;T;T;T;T
Sift4G	Benign	0.52	T;T;T;T;T;T;T
Polyphen		0.080	B;B;.;B;.;B;.
Vest4		0.43
MutPred		0.29		Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);
MVP		0.81
MPC		0.081
ClinPred		0.66	D
GERP RS		6.0
Varity_R		0.089
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr7-89856615;