Variant 7-90227139-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001244944.2(STEAP2):c.661A>G(p.Ser221Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000109 in 1,613,758 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000078 ( 2 hom. )

Consequence

STEAP2
NM_001244944.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.26

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008568853).

BP6

Variant 7-90227139-A-G is Benign according to our data. Variant chr7-90227139-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3041808.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STEAP2	NM_001244944.2 linkuse as main transcript	c.661A>G	p.Ser221Gly	missense_variant	4/6	ENST00000394621.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STEAP2	ENST00000394621.7 linkuse as main transcript	c.661A>G	p.Ser221Gly	missense_variant	4/6	1	NM_001244944.2	P1	Q8NFT2-1

Frequencies

GnomAD3 genomes

AF:

0.000408

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000275

AC:

AN:

250760

Hom.:

AF XY:

0.000295

AC XY:

AN XY:

135532

show subpopulations

Gnomad AFR exome

AF:

0.000739

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00288

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000780

AC:

114

AN:

1461494

Hom.:

Cov.:

AF XY:

0.0000605

AC XY:

AN XY:

727058

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00126

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000712

GnomAD4 genome

AF:

0.000407

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00309

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000168

Hom.:

Bravo

AF:

0.000491

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000247

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

STEAP2-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 17, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0044

T;T;.;T;.;T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.85

M_CAP

Benign

0.0053

MetaRNN

Benign

0.0086

T;T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.075

N;N;N;N;N;.;N

MutationTaster

Benign

0.74

D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

1.7

N;N;N;N;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.40

T;T;T;T;T;T;T

Sift4G

Benign

0.20

T;T;T;T;T;T;T

Polyphen

0.0

B;B;.;B;.;B;.

Vest4

0.26

MVP

0.18

MPC

0.067

ClinPred

0.030

GERP RS

5.9

Varity_R

0.11

gMVP

0.74

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over