2-65379519-T-C

Variant names:

• chr2-65379519-T-C
• rs1194849
• NM_181784.3:c.27-34623A>G

Variant summary

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

The NM_181784.3(SPRED2):​c.27-34623A>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 NM_181784.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.795
• Publications: 11 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

ENSG00000232693 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SPRED2	NM_181784.3	c.27-34623A>G		intron_variant	Intron 1 of 5	ENST00000356388.9	NP_861449.2
SPRED2	XM_047443709.1	c.-35+1107A>G		intron_variant	Intron 1 of 5		XP_047299665.1
SPRED2	XM_005264200.6	c.27-34623A>G		intron_variant	Intron 1 of 6		XP_005264257.2
SPRED2	XM_005264202.6	c.27-34623A>G		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.27-34623A>G		intron_variant	Intron 1 of 5	1	NM_181784.3	ENSP00000348753.4
SPRED2	ENST00000440972.1	c.27-34623A>G		intron_variant	Intron 2 of 3	3		ENSP00000406481.1
ENSG00000232693	ENST00000419244.2	n.60+1107A>G		intron_variant	Intron 1 of 3	3
SPRED2	ENST00000426832.2	n.27-34623A>G		intron_variant	Intron 1 of 7	3		ENSP00000414551.2

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

African (AFR) AF: 0.645 AC: 26746 AN: 41490

American (AMR) AF: 0.400 AC: 6116 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1612 AN: 3468

East Asian (EAS) AF: 0.217 AC: 1120 AN: 5172

South Asian (SAS) AF: 0.375 AC: 1804 AN: 4816

European-Finnish (FIN) AF: 0.401 AC: 4237 AN: 10554

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 30060 AN: 67944

Other (OTH) AF: 0.483 AC: 1019 AN: 2110

Alfa AF: 0.460 Hom.: 51122

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
PhyloP100		0.80
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: rs1194849; hg19: chr2-65606653;