2-174337218-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The NM_001145250.2(SP9):​c.1133A>G​(p.Glu378Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Consequence

SP9
NM_001145250.2 missense

Scores

6
6
7

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 5.41
Variant links:
Genes affected
SP9 (HGNC:30690): (Sp9 transcription factor) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-174337218-A-G is Pathogenic according to our data. Variant chr2-174337218-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 1297467.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SP9NM_001145250.2 linkuse as main transcriptc.1133A>G p.Glu378Gly missense_variant 2/2 ENST00000394967.3 NP_001138722.1 P0CG40

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SP9ENST00000394967.3 linkuse as main transcriptc.1133A>G p.Glu378Gly missense_variant 2/25 NM_001145250.2 ENSP00000378418.2 P0CG40
ENSG00000280414ENST00000624790.1 linkuse as main transcriptn.349T>C non_coding_transcript_exon_variant 1/16

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Hypotonia;C0151611:EEG abnormality;C0543888:Epileptic encephalopathy;C3714756:Intellectual disability Pathogenic:1
Likely pathogenic, no assertion criteria providedclinical testingGenetics Department, University Hospital of Angers-- -
SP9-associated disorder Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingInstitute of Human Genetics, University of Leipzig Medical CenterJan 16, 2024Criteria applied: PS2,PS3,PM1,PM5,PM2_SUP -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Benign
-0.091
T
BayesDel_noAF
Benign
-0.37
CADD
Pathogenic
34
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
T
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.021
T
MetaRNN
Uncertain
0.43
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.065
N
PrimateAI
Pathogenic
0.94
D
PROVEAN
Pathogenic
-6.5
D
REVEL
Uncertain
0.37
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.45
MutPred
0.53
Gain of MoRF binding (P = 0.0275);
MVP
0.14
MPC
1.5
ClinPred
0.99
D
GERP RS
3.0
Varity_R
0.66
gMVP
0.89

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-175201946; API