chr2-65371166-T-A

Variant names:

• chr2-65371166-T-A
• rs1858037
• NM_181784.3:c.27-26270A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181784.3(SPRED2):​c.27-26270A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,006 control chromosomes in the GnomAD database, including 9,690 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 0.32 (9690 hom., cov: 32)
• Consequence: SPRED2 NM_181784.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140
• Publications: 37 publications found

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]

SPRED2 Gene-Disease associations (from GenCC):

• Noonan syndrome 14

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181784.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRED2	NM_181784.3	MANE Select	c.27-26270A>T		intron	N/A	NP_861449.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRED2	ENST00000356388.9	TSL:1 MANE Select	c.27-26270A>T		intron	N/A	ENSP00000348753.4
	SPRED2	ENST00000452315.5	TSL:1	c.71+6447A>T		intron	N/A	ENSP00000390595.1
	SPRED2	ENST00000440972.1	TSL:3	c.27-26270A>T		intron	N/A	ENSP00000406481.1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48734 AN: 151888 Hom.: 9683 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.321 AC: 48759 AN: 152006 Hom.: 9690 Cov.: 32 AF XY: 0.329 AC XY: 24447 AN XY: 74308

African (AFR) AF: 0.125 AC: 5173 AN: 41476

American (AMR) AF: 0.489 AC: 7457 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1454 AN: 3468

East Asian (EAS) AF: 0.781 AC: 4032 AN: 5164

South Asian (SAS) AF: 0.591 AC: 2845 AN: 4812

European-Finnish (FIN) AF: 0.283 AC: 2991 AN: 10552

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23652 AN: 67964

Other (OTH) AF: 0.365 AC: 768 AN: 2104

Alfa AF: 0.327 Hom.: 1100

Bravo AF: 0.325

Asia WGS AF: 0.600 AC: 2083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.55
PhyloP100		-0.014
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1858037; hg19: chr2-65598300;