2-65379519-T-C

Position:

• chr2-65379519-T-C

Variant summary

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

The ENST00000356388.9(SPRED2):​c.27-34623A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 152,042 control chromosomes in the GnomAD database, including 18,614 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 0.48 (18614 hom., cov: 32)
• Consequence: SPRED2 ENST00000356388.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.795

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPRED2	NM_181784.3	c.27-34623A>G		intron_variant		ENST00000356388.9	NP_861449.2
SPRED2	XM_005264200.6	c.27-34623A>G		intron_variant			XP_005264257.2
SPRED2	XM_005264202.6	c.27-34623A>G		intron_variant			XP_005264259.1
SPRED2	XM_047443709.1	c.-35+1107A>G		intron_variant			XP_047299665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPRED2	ENST00000356388.9	c.27-34623A>G		intron_variant		1	NM_181784.3	ENSP00000348753	P4
	ENST00000419244.2	n.60+1107A>G		intron_variant, non_coding_transcript_variant		3
SPRED2	ENST00000440972.1	c.27-34623A>G		intron_variant		3		ENSP00000406481

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73071 AN: 151924 Hom.: 18570 Cov.: 32

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.481 AC: 73169 AN: 152042 Hom.: 18614 Cov.: 32 AF XY: 0.475 AC XY: 35274 AN XY: 74330

Gnomad4 AFR AF: 0.645

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.483

Alfa AF: 0.450 Hom.: 31722

Bravo AF: 0.490

Asia WGS AF: 0.370 AC: 1289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1194849; hg19: chr2-65606653;