rs17534670

chr2-65388294-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181784.3(SPRED2):c.27-43398C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,146 control chromosomes in the GnomAD database, including 16,660 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (16660 hom., cov: 32)
• Consequence: SPRED2 NM_181784.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.558

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPRED2	NM_181784.3	c.27-43398C>T		intron_variant		ENST00000356388.9
SPRED2	XM_005264200.6	c.27-43398C>T		intron_variant
SPRED2	XM_005264202.6	c.27-43398C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPRED2	ENST00000356388.9	c.27-43398C>T		intron_variant		1	NM_181784.3	P4
SPRED2	ENST00000440972.1	c.27-43398C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65538 AN: 152028 Hom.: 16656 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.443

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.431 AC: 65555 AN: 152146 Hom.: 16660 Cov.: 32 AF XY: 0.440 AC XY: 32755 AN XY: 74380

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.560

Gnomad4 NFE AF: 0.509

Gnomad4 OTH AF: 0.444

Alfa AF: 0.497 Hom.: 9595

Bravo AF: 0.414

Asia WGS AF: 0.614 AC: 2134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	15
Dann	Benign	0.89

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17534670; hg19: chr2-65615428;