Variant 2-65313866-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_181784.3(SPRED2):c.892C>T(p.Arg298Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000173 in 1,610,598 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

SPRED2
NM_181784.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.95

Variant links:

Genes affected

SPRED2 (HGNC:17722): (sprouty related EVH1 domain containing 2) SPRED2 is a member of the Sprouty (see SPRY1; MIM 602465)/SPRED family of proteins that regulate growth factor-induced activation of the MAP kinase cascade (see MAPK1; MIM 176948) (Nonami et al., 2004 [PubMed 15465815]).[supplied by OMIM, Mar 2008]

SPRED2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPRED2	NM_181784.3 linkuse as main transcript	c.892C>T	p.Arg298Trp	missense_variant	6/6	ENST00000356388.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPRED2	ENST00000356388.9 linkuse as main transcript	c.892C>T	p.Arg298Trp	missense_variant	6/6	1	NM_181784.3	P4	Q7Z698-1
SPRED2	ENST00000452315.5 linkuse as main transcript	c.937C>T	p.Arg313Trp	missense_variant	6/6	1
SPRED2	ENST00000443619.6 linkuse as main transcript	c.883C>T	p.Arg295Trp	missense_variant	6/6	2		A1	Q7Z698-2
SPRED2	ENST00000421087.5 linkuse as main transcript	c.538C>T	p.Arg180Trp	missense_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000692

AC:

AN:

245750

Hom.:

AF XY:

0.0000598

AC XY:

AN XY:

133736

show subpopulations

Gnomad AFR exome

AF:

0.0000640

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000134

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000182

AC:

265

AN:

1458402

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

130

AN XY:

725686

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000398

Gnomad4 NFE exome

AF:

0.000229

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000196

Hom.:

Bravo

AF:

0.000106

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000660

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2023

The c.892C>T (p.R298W) alteration is located in exon 6 (coding exon 6) of the SPRED2 gene. This alteration results from a C to T substitution at nucleotide position 892, causing the arginine (R) at amino acid position 298 to be replaced by a tryptophan (W). 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

0.16

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.22

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.61

D;.;T;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.92

LIST_S2

Pathogenic

0.97

D;D;D;D

M_CAP

Benign

0.084

MetaRNN

Uncertain

0.55

D;D;D;D

MetaSVM

Uncertain

0.016

MutationAssessor

Uncertain

2.6

M;.;.;.

MutationTaster

Benign

0.98

D;D

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-4.0

D;D;D;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.0030

D;D;.;.

Polyphen

1.0

D;.;.;.

Vest4

0.14

MVP

0.92

MPC

1.8

ClinPred

0.79

GERP RS

3.9

Varity_R

0.21

gMVP

0.37

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