2-65313808-T-C

Variant names:

• chr2-65313808-T-C
• rs936514564
• NM_181784.3:c.950A>G

Variant summary

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

The NM_181784.3(SPRED2):​c.950A>G​(p.Asn317Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,461,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N317I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: SPRED2 NM_181784.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.14

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=0.2162332).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPRED2	NM_181784.3	c.950A>G	p.Asn317Ser	missense_variant	Exon 6 of 6	ENST00000356388.9	NP_861449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPRED2	ENST00000356388.9	c.950A>G	p.Asn317Ser	missense_variant	Exon 6 of 6	1	NM_181784.3	ENSP00000348753.4
SPRED2	ENST00000452315.5	c.995A>G	p.Asn332Ser	missense_variant	Exon 6 of 6	1		ENSP00000390595.1
SPRED2	ENST00000443619.6	c.941A>G	p.Asn314Ser	missense_variant	Exon 6 of 6	2		ENSP00000393697.2
SPRED2	ENST00000421087.5	c.596A>G	p.Asn199Ser	missense_variant	Exon 3 of 3	3		ENSP00000407627.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250560 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135670

Gnomad AFR exome AF: 0.00

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: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000178 AC: 26 AN: 1461592 Hom.: 0 Cov.: 34 AF XY: 0.0000179 AC XY: 13 AN XY: 727128

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 NFE exome AF: 0.0000234

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.46	T;.;T;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.030
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.76	N;.;.;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.4	N;N;N;N
REVEL	Benign	0.079
Sift	Benign	0.30	T;T;T;T
Sift4G	Benign	0.60	T;T;.;.
Polyphen		0.0030	B;.;.;.
Vest4		0.11
MutPred		0.34		Loss of loop (P = 0.0112);.;.;.;
MVP		0.82
MPC		0.73
ClinPred		0.25	T
GERP RS		4.6
Varity_R		0.083
gMVP		0.33

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

Other links and lift over

dbSNP: rs936514564; hg19: chr2-65540942;