2-174337218-A-G
Position:
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
NM_001145250.2 missense
Scores
6
6
7
Clinical Significance
Conservation
PhyloP100: 5.41
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]
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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 |
---|---|---|---|---|---|---|---|---|
SP9 | NM_001145250.2 | c.1133A>G | p.Glu378Gly | missense_variant | 2/2 | ENST00000394967.3 | NP_001138722.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SP9 | ENST00000394967.3 | c.1133A>G | p.Glu378Gly | missense_variant | 2/2 | 5 | NM_001145250.2 | ENSP00000378418.2 | ||
ENSG00000280414 | ENST00000624790.1 | n.349T>C | non_coding_transcript_exon_variant | 1/1 | 6 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome Cov.: 33
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 provided | clinical testing | Genetics Department, University Hospital of Angers | - | - - |
SP9-associated disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Jan 16, 2024 | Criteria applied: PS2,PS3,PM1,PM5,PM2_SUP - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of MoRF binding (P = 0.0275);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.