rs779268703

Variant names:

• chr17-47916697-A-G
• rs779268703
• NM_003110.6:c.626A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003110.6(SP2):​c.626A>G​(p.Asn209Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,613,416 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: SP2 NM_003110.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.23
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003110.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP2	NM_003110.6	MANE Select	c.626A>G	p.Asn209Ser	missense	Exon 3 of 7	NP_003101.3
	SP2-AS1	NR_103856.1		n.189+1755T>C		intron	N/A
	SP2-AS1	NR_103857.1		n.178+1755T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP2	ENST00000376741.5	TSL:1 MANE Select	c.626A>G	p.Asn209Ser	missense	Exon 3 of 7	ENSP00000365931.4	Q02086-1
	SP2	ENST00000884863.1		c.581A>G	p.Asn194Ser	missense	Exon 3 of 7	ENSP00000554922.1
	SP2	ENST00000884862.1		c.417+209A>G		intron	N/A	ENSP00000554921.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 250974 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1461276 Hom.: 0 Cov.: 50 AF XY: 0.0000138 AC XY: 10 AN XY: 726854

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111546

Other (OTH) AF: 0.0000166 AC: 1 AN: 60356

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152140 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74318

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0057	T
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.2
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.085
Sift	Benign	0.23	T
Sift4G	Benign	0.13	T
Polyphen		0.77	P
Vest4		0.61
MutPred		0.30		Loss of sheet (P = 0.0104)
MVP		0.59
MPC		0.80
ClinPred		0.42	T
GERP RS		5.4
Varity_R		0.042
gMVP		0.52
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs779268703; hg19: chr17-45994063;