Variant rs504122 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005842.4(SPRY2):c.316C>T(p.Pro106Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,613,932 control chromosomes in the GnomAD database, including 105,010 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.29 ( 7776 hom., cov: 32)

Exomes 𝑓: 0.36 ( 97234 hom. )

Consequence

SPRY2
NM_005842.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.01

Variant links:

Genes affected

SPRY2 (HGNC:11270): (sprouty RTK signaling antagonist 2) This gene encodes a protein belonging to the sprouty family. The encoded protein contains a carboxyl-terminal cysteine-rich domain essential for the inhibitory activity on receptor tyrosine kinase signaling proteins and is required for growth factor stimulated translocation of the protein to membrane ruffles. In primary dermal endothelial cells this gene is transiently upregulated in response to fibroblast growth factor two. This protein is indirectly involved in the non-cell autonomous inhibitory effect on fibroblast growth factor two signaling. The protein interacts with Cas-Br-M (murine) ectropic retroviral transforming sequence, and can function as a bimodal regulator of epidermal growth factor receptor/mitogen-activated protein kinase signaling. This protein may play a role in alveoli branching during lung development as shown by a similar mouse protein. [provided by RefSeq, Jul 2008]

SPRY2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014727116).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SPRY2	NM_005842.4 linkuse as main transcript	c.316C>T	p.Pro106Ser	missense_variant	2/2	ENST00000377104.4
SPRY2	NM_001318536.1 linkuse as main transcript	c.316C>T	p.Pro106Ser	missense_variant	2/2
SPRY2	NM_001318537.1 linkuse as main transcript	c.316C>T	p.Pro106Ser	missense_variant	2/2
SPRY2	NM_001318538.1 linkuse as main transcript	c.316C>T	p.Pro106Ser	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPRY2	ENST00000377104.4 linkuse as main transcript	c.316C>T	p.Pro106Ser	missense_variant	2/2	1	NM_005842.4	P1
SPRY2	ENST00000377102.5 linkuse as main transcript	c.316C>T	p.Pro106Ser	missense_variant	2/2	1		P1

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43850

AN:

151966

Hom.:

7763

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0703

Gnomad AMI

AF:

0.390

Gnomad AMR

AF:

0.423

Gnomad ASJ

AF:

0.329

Gnomad EAS

AF:

0.451

Gnomad SAS

AF:

0.335

Gnomad FIN

AF:

0.373

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.358

Gnomad OTH

AF:

0.326

GnomAD3 exomes

AF:

0.367

AC:

92225

AN:

251408

Hom.:

18303

AF XY:

0.366

AC XY:

49712

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.0660

Gnomad AMR exome

AF:

0.520

Gnomad ASJ exome

AF:

0.316

Gnomad EAS exome

AF:

0.472

Gnomad SAS exome

AF:

0.355

Gnomad FIN exome

AF:

0.370

Gnomad NFE exome

AF:

0.353

Gnomad OTH exome

AF:

0.370

GnomAD4 exome

AF:

0.360

AC:

525742

AN:

1461848

Hom.:

97234

Cov.:

AF XY:

0.359

AC XY:

261340

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0565

Gnomad4 AMR exome

AF:

0.511

Gnomad4 ASJ exome

AF:

0.321

Gnomad4 EAS exome

AF:

0.423

Gnomad4 SAS exome

AF:

0.357

Gnomad4 FIN exome

AF:

0.359

Gnomad4 NFE exome

AF:

0.362

Gnomad4 OTH exome

AF:

0.357

GnomAD4 genome

AF:

0.289

AC:

43878

AN:

152084

Hom.:

7776

Cov.:

AF XY:

0.294

AC XY:

21843

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.0701

Gnomad4 AMR

AF:

0.424

Gnomad4 ASJ

AF:

0.329

Gnomad4 EAS

AF:

0.451

Gnomad4 SAS

AF:

0.339

Gnomad4 FIN

AF:

0.373

Gnomad4 NFE

AF:

0.358

Gnomad4 OTH

AF:

0.323

Alfa

AF:

0.344

Hom.:

18331

Bravo

AF:

0.286

TwinsUK

AF:

0.359

AC:

1331

ALSPAC

AF:

0.354

AC:

1366

ESP6500AA

AF:

0.0803

AC:

354

ESP6500EA

AF:

0.359

AC:

3087

ExAC

AF:

0.354

AC:

42968

Asia WGS

AF:

0.329

AC:

1146

AN:

3478

EpiCase

AF:

0.346

EpiControl

AF:

0.359

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

Cadd

Benign

Dann

Benign

0.94

DEOGEN2

Benign

0.34

T;T

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.48

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.39

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.14

Sift

Benign

0.097

T;T

Sift4G

Benign

0.074

T;T

Polyphen

0.0

B;B

Vest4

0.072

MPC

0.47

ClinPred

0.0061

GERP RS

0.64

Varity_R

0.069

gMVP

0.45

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over