rs504122

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Publications

42 publications found

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 Gene-Disease associations (from GenCC):

IgA nephropathy, susceptibility to, 3
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
Tourette syndrome
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

SPRY2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SPRY2	NM_005842.4 link	c.316C>T	p.Pro106Ser	missense_variant	Exon 2 of 2	ENST00000377104.4	NP_005833.1	O43597
SPRY2	NM_001318536.1 link	c.316C>T	p.Pro106Ser	missense_variant	Exon 2 of 2		NP_001305465.1	O43597
SPRY2	NM_001318537.1 link	c.316C>T	p.Pro106Ser	missense_variant	Exon 2 of 2		NP_001305466.1	O43597
SPRY2	NM_001318538.1 link	c.316C>T	p.Pro106Ser	missense_variant	Exon 2 of 2		NP_001305467.1	O43597

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPRY2	ENST00000377104.4 link	c.316C>T	p.Pro106Ser	missense_variant	Exon 2 of 2	1	NM_005842.4	ENSP00000366308.3		O43597
SPRY2	ENST00000377102.5 link	c.316C>T	p.Pro106Ser	missense_variant	Exon 2 of 2	1		ENSP00000366306.1		O43597

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

GnomAD2 exomes

AF:

0.367

AC:

92225

AN:

251408

AF XY:

0.366

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 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

African (AFR)

AF:

0.0565

AC:

1892

AN:

33480

American (AMR)

AF:

0.511

AC:

22845

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.321

AC:

8401

AN:

26136

East Asian (EAS)

AF:

0.423

AC:

16798

AN:

39700

South Asian (SAS)

AF:

0.357

AC:

30773

AN:

86258

European-Finnish (FIN)

AF:

0.359

AC:

19169

AN:

53392

Middle Eastern (MID)

AF:

0.348

AC:

2009

AN:

5768

European-Non Finnish (NFE)

AF:

0.362

AC:

402298

AN:

1111994

Other (OTH)

AF:

0.357

AC:

21557

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

24109

48219

72328

96438

120547

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12862

25724

38586

51448

64310

<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

AF:

0.289

AC:

43878

AN:

152084

Hom.:

7776

Cov.:

AF XY:

0.294

AC XY:

21843

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.0701

AC:

2911

AN:

41548

American (AMR)

AF:

0.424

AC:

6470

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.329

AC:

1140

AN:

3468

East Asian (EAS)

AF:

0.451

AC:

2323

AN:

5150

South Asian (SAS)

AF:

0.339

AC:

1632

AN:

4820

European-Finnish (FIN)

AF:

0.373

AC:

3934

AN:

10558

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.358

AC:

24321

AN:

67966

Other (OTH)

AF:

0.323

AC:

681

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1481

2962

4442

5923

7404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

452

904

1356

1808

2260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.330

Hom.:

29431

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

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.34

T;T

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.55

.;T

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.6

L;L

PhyloP100

1.0

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

Mutation Taster

=99/1

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over