7-90227329-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001244944.2(STEAP2):c.851A>G(p.Tyr284Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00487 in 1,613,912 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0041 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0050 (22 hom.)
• Consequence: STEAP2 NM_001244944.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.26

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014110327).
• BP6: Variant 7-90227329-A-G is Benign according to our data. Variant chr7-90227329-A-G is described in ClinVar as [Benign]. Clinvar id is 3042658.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STEAP2	NM_001244944.2	c.851A>G	p.Tyr284Cys	missense_variant	4/6	ENST00000394621.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STEAP2	ENST00000394621.7	c.851A>G	p.Tyr284Cys	missense_variant	4/6	1	NM_001244944.2	P1

Frequencies

GnomAD3 genomes AF: 0.00406 AC: 617 AN: 152152 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00572

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00417 AC: 1047 AN: 251110 Hom.: 7 AF XY: 0.00401 AC XY: 544 AN XY: 135720

Gnomad AFR exome AF: 0.000985

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.0141

Gnomad NFE exome AF: 0.00588

Gnomad OTH exome AF: 0.00343

GnomAD4 exome AF: 0.00496 AC: 7248 AN: 1461642 Hom.: 22 Cov.: 35 AF XY: 0.00480 AC XY: 3487 AN XY: 727120

Gnomad4 AFR exome AF: 0.000807

Gnomad4 AMR exome AF: 0.00141

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.0121

Gnomad4 NFE exome AF: 0.00561

Gnomad4 OTH exome AF: 0.00439

GnomAD4 genome AF: 0.00405 AC: 617 AN: 152270 Hom.: 2 Cov.: 33 AF XY: 0.00436 AC XY: 325 AN XY: 74466

Gnomad4 AFR AF: 0.000722

Gnomad4 AMR AF: 0.00281

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0135

Gnomad4 NFE AF: 0.00572

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00469 Hom.: 5

Bravo AF: 0.00322

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00415 AC: 16

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00581 AC: 50

ExAC AF: 0.00445 AC: 540

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00567

EpiControl AF: 0.00338

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

STEAP2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 26, 2019

This variant is classified as 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	0.075
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Uncertain	0.13
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D;D;.;D;.;D;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.93	D
MetaRNN	Benign	0.014	T;T;T;T;T;T;T
MetaSVM	Uncertain	0.42	D
MutationAssessor	Benign	1.9	L;L;L;L;L;.;L
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.6	D;D;D;D;D;D;D
REVEL	Uncertain	0.61
Sift	Uncertain	0.024	D;D;D;D;D;D;D
Sift4G	Uncertain	0.049	D;D;D;D;T;T;D
Polyphen		1.0	D;D;.;D;.;D;.
Vest4		0.79
MVP		0.99
MPC		0.45
ClinPred		0.032	T
GERP RS		6.0
Varity_R		0.29
gMVP		0.69

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

LitVar

Other links and lift over

dbSNP: rs138124501; hg19: chr7-89856643; COSMIC: COSV55294277; COSMIC: COSV55294277;