2-65381775-C-T

Variant names:

• chr2-65381775-C-T
• rs1876518
• NM_181784.3:c.27-36879G>A

Variant summary

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

The NM_181784.3(SPRED2):​c.27-36879G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 152,096 control chromosomes in the GnomAD database, including 15,153 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 0.44 (15153 hom., cov: 32)
• Consequence: SPRED2 NM_181784.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255
• Publications: 35 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPRED2	NM_181784.3	c.27-36879G>A		intron_variant	Intron 1 of 5	ENST00000356388.9	NP_861449.2
SPRED2	XM_047443709.1	c.-1184G>A		5_prime_UTR_variant	Exon 1 of 6		XP_047299665.1
SPRED2	XM_005264200.6	c.27-36879G>A		intron_variant	Intron 1 of 6		XP_005264257.2
SPRED2	XM_005264202.6	c.27-36879G>A		intron_variant	Intron 1 of 5		XP_005264259.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPRED2	ENST00000356388.9	c.27-36879G>A		intron_variant	Intron 1 of 5	1	NM_181784.3	ENSP00000348753.4
SPRED2	ENST00000440972.1	c.27-36879G>A		intron_variant	Intron 2 of 3	3		ENSP00000406481.1
SPRED2	ENST00000426832.2	n.27-36879G>A		intron_variant	Intron 1 of 7	3		ENSP00000414551.2

Frequencies

GnomAD3 genomes AF: 0.441 AC: 67053 AN: 151978 Hom.: 15126 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.441 AC: 67130 AN: 152096 Hom.: 15153 Cov.: 32 AF XY: 0.436 AC XY: 32444 AN XY: 74348

African (AFR) AF: 0.507 AC: 21034 AN: 41498

American (AMR) AF: 0.383 AC: 5851 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1607 AN: 3472

East Asian (EAS) AF: 0.217 AC: 1122 AN: 5170

South Asian (SAS) AF: 0.373 AC: 1797 AN: 4816

European-Finnish (FIN) AF: 0.403 AC: 4252 AN: 10560

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

European-Non Finnish (NFE) AF: 0.442 AC: 30037 AN: 67964

Other (OTH) AF: 0.463 AC: 978 AN: 2114

Alfa AF: 0.440 Hom.: 50968

Bravo AF: 0.444

Asia WGS AF: 0.358 AC: 1245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.3
DANN	Benign	0.74
PhyloP100		-0.26
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: rs1876518; hg19: chr2-65608909;