2-65368452-G-A

Position:

• chr2-65368452-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.27-23556C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 152,076 control chromosomes in the GnomAD database, including 23,004 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 0.55 (23004 hom., 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• 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	Protein	UniProt
SPRED2	NM_181784.3	c.27-23556C>T		intron_variant		ENST00000356388.9	NP_861449.2
SPRED2	XM_005264200.6	c.27-23556C>T		intron_variant			XP_005264257.2
SPRED2	XM_005264202.6	c.27-23556C>T		intron_variant			XP_005264259.1
SPRED2	XM_047443709.1	c.-35+12174C>T		intron_variant			XP_047299665.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83153 AN: 151958 Hom.: 22963 Cov.: 33

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.547 AC: 83250 AN: 152076 Hom.: 23004 Cov.: 33 AF XY: 0.552 AC XY: 41050 AN XY: 74336

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.594

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.560

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.526

Alfa AF: 0.520 Hom.: 24764

Bravo AF: 0.547

Asia WGS AF: 0.643 AC: 2233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.3
DANN	Benign	0.43

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;