2-65368452-G-T

Position:

• chr2-65368452-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181784.3(SPRED2):​c.27-23556C>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SPRED2 NM_181784.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.759

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPRED2	NM_181784.3	c.27-23556C>A		intron_variant		ENST00000356388.9	NP_861449.2
SPRED2	XM_005264200.6	c.27-23556C>A		intron_variant			XP_005264257.2
SPRED2	XM_005264202.6	c.27-23556C>A		intron_variant			XP_005264259.1
SPRED2	XM_047443709.1	c.-35+12174C>A		intron_variant			XP_047299665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPRED2	ENST00000356388.9	c.27-23556C>A		intron_variant		1	NM_181784.3	ENSP00000348753	P4
SPRED2	ENST00000452315.5	c.71+9161C>A		intron_variant		1		ENSP00000390595
SPRED2	ENST00000440972.1	c.27-23556C>A		intron_variant		3		ENSP00000406481

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.7
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs934734; hg19: chr2-65595586;