2-65314177-G-A

Position:

• chr2-65314177-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_181784.3(SPRED2):​c.589-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000874 in 1,570,134 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00083 (10 hom.)
• Consequence: SPRED2 NM_181784.3 splice_region, intron
• Scores: Splicing: ADA: 0.00004326
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.326

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-65314177-G-A is Benign according to our data. Variant chr2-65314177-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2651009.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPRED2	NM_181784.3	c.589-8C>T		splice_region_variant, intron_variant		ENST00000356388.9	NP_861449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPRED2	ENST00000356388.9	c.589-8C>T		splice_region_variant, intron_variant		1	NM_181784.3	ENSP00000348753.4
SPRED2	ENST00000452315.5	c.634-8C>T		splice_region_variant, intron_variant		1		ENSP00000390595.1
SPRED2	ENST00000443619.6	c.580-8C>T		splice_region_variant, intron_variant		2		ENSP00000393697.2
SPRED2	ENST00000421087.5	c.235-8C>T		splice_region_variant, intron_variant		3		ENSP00000407627.1

Frequencies

GnomAD3 genomes AF: 0.00131 AC: 199 AN: 152204 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0125

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00153 AC: 341 AN: 223576 Hom.: 3 AF XY: 0.00172 AC XY: 208 AN XY: 121228

Gnomad AFR exome AF: 0.000192

Gnomad AMR exome AF: 0.000100

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000659

Gnomad FIN exome AF: 0.0117

Gnomad NFE exome AF: 0.000797

Gnomad OTH exome AF: 0.000745

GnomAD4 exome AF: 0.000827 AC: 1173 AN: 1417930 Hom.: 10 Cov.: 34 AF XY: 0.000875 AC XY: 612 AN XY: 699098

Gnomad4 AFR exome AF: 0.0000623

Gnomad4 AMR exome AF: 0.000101

Gnomad4 ASJ exome AF: 0.0000417

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000881

Gnomad4 FIN exome AF: 0.00985

Gnomad4 NFE exome AF: 0.000499

Gnomad4 OTH exome AF: 0.000549

GnomAD4 genome AF: 0.00131 AC: 199 AN: 152204 Hom.: 1 Cov.: 33 AF XY: 0.00186 AC XY: 138 AN XY: 74360

Gnomad4 AFR AF: 0.0000724

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0125

Gnomad4 NFE AF: 0.000882

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000835 Hom.: 0

Bravo AF: 0.000302

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2023

SPRED2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.98
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000043
dbscSNV1_RF	Benign	0.0060
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs200299417; hg19: chr2-65541311;