Variant chr2-65313815-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181784.3(SPRED2):c.943A>C(p.Met315Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000162 in 1,613,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

SPRED2
NM_181784.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.58

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.103636056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPRED2	NM_181784.3 linkuse as main transcript	c.943A>C	p.Met315Leu	missense_variant	6/6	ENST00000356388.9	NP_861449.2	Q7Z698-1B3KPL5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SPRED2	ENST00000356388.9 linkuse as main transcript	c.943A>C	p.Met315Leu	missense_variant	6/6	1	NM_181784.3	ENSP00000348753.4	Q7Z698-1
SPRED2	ENST00000452315.5 linkuse as main transcript	c.988A>C	p.Met330Leu	missense_variant	6/6	1		ENSP00000390595.1	C9JG63
SPRED2	ENST00000443619.6 linkuse as main transcript	c.934A>C	p.Met312Leu	missense_variant	6/6	2		ENSP00000393697.2	Q7Z698-2
SPRED2	ENST00000421087.5 linkuse as main transcript	c.589A>C	p.Met197Leu	missense_variant	3/3	3		ENSP00000407627.1	H7C2T4

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000176

AC:

AN:

250294

Hom.:

AF XY:

0.000170

AC XY:

AN XY:

135566

show subpopulations

Gnomad AFR exome

AF:

0.0000618

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:

0.0000470

Gnomad NFE exome

AF:

0.000362

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000170

AC:

248

AN:

1461472

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

116

AN XY:

727056

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:

0.00

Gnomad4 FIN exome

AF:

0.0000943

Gnomad4 NFE exome

AF:

0.000206

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000171

Hom.:

Bravo

AF:

0.000125

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000329

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Dec 18, 2023

The c.943A>C (p.M315L) alteration is located in exon 6 (coding exon 6) of the SPRED2 gene. This alteration results from a A to C substitution at nucleotide position 943, causing the methionine (M) at amino acid position 315 to be replaced by a leucine (L). 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

0.18

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.27

T;.;T;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.038

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.82

T;T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.10

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

L;.;.;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.84

N;N;N;N

REVEL

Benign

0.13

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.85

T;T;.;.

Polyphen

0.046

B;.;.;.

Vest4

0.18

MutPred

0.49

Loss of loop (P = 0.0112);.;.;.;

MVP

0.75

MPC

0.82

ClinPred

0.11

GERP RS

5.8

Varity_R

0.36

gMVP

0.32

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