rs797045587
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014491.4(FOXP2):c.282G>A(p.Met94Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
FOXP2
NM_014491.4 missense
NM_014491.4 missense
Scores
8
7
4
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 10.0
Genes affected
FOXP2 (HGNC:13875): (forkhead box P2) This gene encodes a member of the forkhead/winged-helix (FOX) family of transcription factors. It is expressed in fetal and adult brain as well as in several other organs such as the lung and gut. The protein product contains a FOX DNA-binding domain and a large polyglutamine tract and is an evolutionarily conserved transcription factor, which may bind directly to approximately 300 to 400 gene promoters in the human genome to regulate the expression of a variety of genes. This gene is required for proper development of speech and language regions of the brain during embryogenesis, and may be involved in a variety of biological pathways and cascades that may ultimately influence language development. Mutations in this gene cause speech-language disorder 1 (SPCH1), also known as autosomal dominant speech and language disorder with orofacial dyspraxia. Multiple alternative transcripts encoding different isoforms have been identified in this gene.[provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461812Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727216
GnomAD4 exome
AF:
AC:
1
AN:
1461812
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
727216
Gnomad4 AFR exome
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Gnomad4 AMR exome
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Gnomad4 ASJ exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 NFE exome
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Gnomad4 OTH exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;.;D;.;T;.;D;T;.;.;T;.;.;T
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;.;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Benign
.;.;.;N;N;.;.;N;.;N;.;.;N;.;.
PrimateAI
Pathogenic
T
PROVEAN
Uncertain
.;.;.;D;D;N;D;D;N;D;N;.;N;D;N
REVEL
Uncertain
Sift
Pathogenic
.;.;.;D;D;D;D;D;D;D;D;.;D;D;D
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
0.97, 0.53, 0.89, 0.66
.;.;.;D;.;P;P;D;.;.;.;.;P;.;P
Vest4
MutPred
Gain of catalytic residue at P96 (P = 0.0327);Gain of catalytic residue at P96 (P = 0.0327);Gain of catalytic residue at P96 (P = 0.0327);Gain of catalytic residue at P96 (P = 0.0327);Gain of catalytic residue at P96 (P = 0.0327);.;.;Gain of catalytic residue at P96 (P = 0.0327);Gain of catalytic residue at P96 (P = 0.0327);Gain of catalytic residue at P96 (P = 0.0327);.;Gain of catalytic residue at P96 (P = 0.0327);Gain of catalytic residue at P96 (P = 0.0327);Gain of catalytic residue at P96 (P = 0.0327);.;
MVP
0.90
MPC
0.71
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.