rs2229358

chr17-47916788-G-Achr17-47916788-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003110.6(SP2):c.717G>A(p.Pro239=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,613,216 control chromosomes in the GnomAD database, including 162,322 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 0.43 (14462 hom., cov: 32)
  • Exomes 𝑓: 0.44 (147860 hom.)
• Consequence: SP2 NM_003110.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.86

Genes affected

SP2 (HGNC:11207): (Sp2 transcription factor) This gene encodes a member of the Sp subfamily of Sp/XKLF transcription factors. Sp family proteins are sequence-specific DNA-binding proteins characterized by an amino-terminal trans-activation domain and three carboxy-terminal zinc finger motifs. This protein contains the least conserved DNA-binding domain within the Sp subfamily of proteins, and its DNA sequence specificity differs from the other Sp proteins. It localizes primarily within subnuclear foci associated with the nuclear matrix, and can activate or in some cases repress expression from different promoters. [provided by RefSeq, Jul 2008]

SP2-AS1 (HGNC:51341): (SP2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-3.86 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SP2	NM_003110.6	c.717G>A	p.Pro239=	synonymous_variant	3/7	ENST00000376741.5
SP2-AS1	NR_103857.1	n.178+1664C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SP2	ENST00000376741.5	c.717G>A	p.Pro239=	synonymous_variant	3/7	1	NM_003110.6	P1
SP2-AS1	ENST00000585280.5	n.174+1664C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65335 AN: 151950 Hom.: 14449 Cov.: 32

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.470

GnomAD3 exomes AF: 0.463 AC: 116318 AN: 251054 Hom.: 28196 AF XY: 0.466 AC XY: 63202 AN XY: 135676

Gnomad AFR exome AF: 0.355

Gnomad AMR exome AF: 0.423

Gnomad ASJ exome AF: 0.502

Gnomad EAS exome AF: 0.760

Gnomad SAS exome AF: 0.489

Gnomad FIN exome AF: 0.449

Gnomad NFE exome AF: 0.435

Gnomad OTH exome AF: 0.477

GnomAD4 exome AF: 0.445 AC: 649742 AN: 1461148 Hom.: 147860 Cov.: 47 AF XY: 0.446 AC XY: 324451 AN XY: 726882

Gnomad4 AFR exome AF: 0.351

Gnomad4 AMR exome AF: 0.426

Gnomad4 ASJ exome AF: 0.501

Gnomad4 EAS exome AF: 0.768

Gnomad4 SAS exome AF: 0.493

Gnomad4 FIN exome AF: 0.450

Gnomad4 NFE exome AF: 0.430

Gnomad4 OTH exome AF: 0.457

GnomAD4 genome AF: 0.430 AC: 65386 AN: 152068 Hom.: 14462 Cov.: 32 AF XY: 0.431 AC XY: 32017 AN XY: 74316

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.759

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.477

Alfa AF: 0.443 Hom.: 35723

Bravo AF: 0.425

Asia WGS AF: 0.593 AC: 2061 AN: 3478

EpiCase AF: 0.449

EpiControl AF: 0.434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.076
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2229358; hg19: chr17-45994154; COSMIC: COSV65063925; COSMIC: COSV65063925;