17-47916761-G-C

Variant names:

• chr17-47916761-G-C
• rs2035223157
• NM_003110.6:c.690G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003110.6(SP2):​c.690G>C​(p.Gln230His) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,112 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SP2 NM_003110.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.97

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP2	NM_003110.6	c.690G>C	p.Gln230His	missense_variant	Exon 3 of 7	ENST00000376741.5	NP_003101.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP2	ENST00000376741.5	c.690G>C	p.Gln230His	missense_variant	Exon 3 of 7	1	NM_003110.6	ENSP00000365931.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461112 Hom.: 0 Cov.: 53 AF XY: 0.00000413 AC XY: 3 AN XY: 726812

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.690G>C (p.Q230H) alteration is located in exon 3 (coding exon 3) of the SP2 gene. This alteration results from a G to C substitution at nucleotide position 690, causing the glutamine (Q) at amino acid position 230 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	.;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;L
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.3	.;N
REVEL	Benign	0.10
Sift	Uncertain	0.0010	.;D
Sift4G	Uncertain	0.0080	D;T
Polyphen		1.0	.;D
Vest4		0.70
MutPred		0.30		.;Gain of sheet (P = 0.0266);
MVP		0.56
MPC		1.5
ClinPred		0.82	D
GERP RS		4.4
Varity_R		0.21
gMVP		0.75

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: rs2035223157; hg19: chr17-45994127;