rs1194849

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-65379519-T-A
• chr2-65379519-T-C
• chr2-65379519-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181784.3(SPRED2):​c.27-34623A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: SPRED2 NM_181784.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.795
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPRED2	NM_181784.3	c.27-34623A>T		intron_variant	Intron 1 of 5	ENST00000356388.9	NP_861449.2
SPRED2	XM_047443709.1	c.-35+1107A>T		intron_variant	Intron 1 of 5		XP_047299665.1
SPRED2	XM_005264200.6	c.27-34623A>T		intron_variant	Intron 1 of 6		XP_005264257.2
SPRED2	XM_005264202.6	c.27-34623A>T		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>T		intron_variant	Intron 1 of 5	1	NM_181784.3	ENSP00000348753.4
SPRED2	ENST00000440972.1	c.27-34623A>T		intron_variant	Intron 2 of 3	3		ENSP00000406481.1
ENSG00000232693	ENST00000419244.2	n.60+1107A>T		intron_variant	Intron 1 of 3	3
SPRED2	ENST00000426832.2	n.27-34623A>T		intron_variant	Intron 1 of 7	3		ENSP00000414551.2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	10
DANN	Benign	0.84
PhyloP100		0.80

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;