2-65313815-T-A

Position:

• chr2-65313815-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181784.3(SPRED2):​c.943A>T​(p.Met315Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: SPRED2 NM_181784.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.58

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]

ACMG classification

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=0.21118814).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPRED2	NM_181784.3	c.943A>T	p.Met315Leu	missense_variant	6/6	ENST00000356388.9	NP_861449.2

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 21, 2023

The c.943A>T (p.M315L) alteration is located in exon 6 (coding exon 6) of the SPRED2 gene. This alteration results from a A to T 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	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Benign	0.75
DEOGEN2	Benign	0.27	T;.;T;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.038
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.82	T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L;.;.;.
PrimateAI	Uncertain	0.64	T
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		0.89	D
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-65540949;