dbSNP rs2229358: SP2:p.Pro239Pro (chr17-47916788-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_003110.6(SP2):c.717G>A(p.Pro239Pro) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.86

Publications

25 publications found

Variant links:

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 links:

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

SP2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SP2	NM_003110.6 link	c.717G>A	p.Pro239Pro	synonymous_variant	Exon 3 of 7	ENST00000376741.5	NP_003101.3	Q02086-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP2	ENST00000376741.5 link	c.717G>A	p.Pro239Pro	synonymous_variant	Exon 3 of 7	1	NM_003110.6	ENSP00000365931.4		Q02086-1

Frequencies

GnomAD3 genomes

AF:

0.430

AC:

65335

AN:

151950

Hom.:

14449

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.463

AC:

116318

AN:

251054

AF XY:

0.466

show subpopulations

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 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.:

AF XY:

0.446

AC XY:

324451

AN XY:

726882

show subpopulations

African (AFR)

AF:

0.351

AC:

11744

AN:

33468

American (AMR)

AF:

0.426

AC:

19034

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.501

AC:

13090

AN:

26106

East Asian (EAS)

AF:

0.768

AC:

30506

AN:

39700

South Asian (SAS)

AF:

0.493

AC:

42507

AN:

86234

European-Finnish (FIN)

AF:

0.450

AC:

24055

AN:

53410

Middle Eastern (MID)

AF:

0.555

AC:

3200

AN:

5768

European-Non Finnish (NFE)

AF:

0.430

AC:

478010

AN:

1111402

Other (OTH)

AF:

0.457

AC:

27596

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

21072

42145

63217

84290

105362

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14644

29288

43932

58576

73220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.430

AC:

65386

AN:

152068

Hom.:

14462

Cov.:

AF XY:

0.431

AC XY:

32017

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.358

AC:

14851

AN:

41468

American (AMR)

AF:

0.432

AC:

6601

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.496

AC:

1721

AN:

3472

East Asian (EAS)

AF:

0.759

AC:

3925

AN:

5174

South Asian (SAS)

AF:

0.476

AC:

2299

AN:

4826

European-Finnish (FIN)

AF:

0.452

AC:

4776

AN:

10570

Middle Eastern (MID)

AF:

0.490

AC:

144

AN:

294

European-Non Finnish (NFE)

AF:

0.437

AC:

29672

AN:

67950

Other (OTH)

AF:

0.477

AC:

1009

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1873

3745

5618

7490

9363

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

620

1240

1860

2480

3100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.438

Hom.:

53870

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

(source)

DANN

Benign

0.74

PhyloP100

-3.9

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over