rs532860603

Variant names:

• chr2-65313841-C-A
• rs532860603
• NM_181784.3:c.917G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-65313841-C-A
• chr2-65313841-C-G
• chr2-65313841-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_181784.3(SPRED2):​c.917G>T​(p.Arg306Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,459,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R306H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SPRED2 NM_181784.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.93

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.784

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPRED2	NM_181784.3	c.917G>T	p.Arg306Leu	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.917G>T	p.Arg306Leu	missense_variant	Exon 6 of 6	1	NM_181784.3	ENSP00000348753.4
SPRED2	ENST00000452315.5	c.962G>T	p.Arg321Leu	missense_variant	Exon 6 of 6	1		ENSP00000390595.1
SPRED2	ENST00000443619.6	c.908G>T	p.Arg303Leu	missense_variant	Exon 6 of 6	2		ENSP00000393697.2
SPRED2	ENST00000421087.5	c.563G>T	p.Arg188Leu	missense_variant	Exon 3 of 3	3		ENSP00000407627.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1459782 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726316

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: 0.00000450

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.62	D;.;T;.
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.78	D;D;D;D
MetaSVM	Uncertain	0.12	D
MutationAssessor	Uncertain	2.8	M;.;.;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-4.2	D;D;D;D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Uncertain	0.013	D;D;.;.
Polyphen		1.0	D;.;.;.
Vest4		0.75
MutPred		0.52		Loss of solvent accessibility (P = 0.0013);.;.;.;
MVP		0.90
MPC		2.1
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.58
gMVP		0.68

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: rs532860603; hg19: chr2-65540975;