Genetic Variant STEAP2:p.Asp139His (chr7-90225497-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001244944.2(STEAP2):c.415G>C(p.Asp139His) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. D139Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

STEAP2
NM_001244944.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.66

Publications

1 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36818382).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001244944.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STEAP2	NM_001244944.2	MANE Select	c.415G>C	p.Asp139His	missense	Exon 3 of 6	NP_001231873.1	Q8NFT2-1
STEAP2	NM_001040665.2		c.415G>C	p.Asp139His	missense	Exon 3 of 6	NP_001035755.1	Q8NFT2-1
STEAP2	NM_152999.4		c.415G>C	p.Asp139His	missense	Exon 2 of 5	NP_694544.2	Q8NFT2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STEAP2	ENST00000394621.7	TSL:1 MANE Select	c.415G>C	p.Asp139His	missense	Exon 3 of 6	ENSP00000378119.2	Q8NFT2-1
STEAP2	ENST00000287908.7	TSL:1	c.415G>C	p.Asp139His	missense	Exon 2 of 5	ENSP00000287908.3	Q8NFT2-1
STEAP2	ENST00000394622.6	TSL:1	c.415G>C	p.Asp139His	missense	Exon 3 of 6	ENSP00000378120.2	Q8NFT2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

250984

AF XY:

0.00000737

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461516

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727030

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.00

AC:

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.00

AC:

AN:

86218

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111840

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.036

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.81

M_CAP

Benign

0.012

MetaRNN

Benign

0.37

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PhyloP100

6.7

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.7

REVEL

Benign

0.11

Sift

Benign

0.073

Sift4G

Benign

0.14

Polyphen

0.17

Vest4

0.45

MutPred

0.47

Loss of solvent accessibility (P = 0.0187)

MVP

0.32

MPC

0.086

ClinPred

0.67

GERP RS

5.7

Varity_R

0.25

gMVP

0.72

Mutation Taster

=61/39

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over