rs760790139
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS2
The NM_000325.6(PITX2):c.916G>T(p.Val306Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,856 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: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
PITX2
NM_000325.6 missense
NM_000325.6 missense
Scores
3
8
8
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.91
Genes affected
PITX2 (HGNC:9005): (paired like homeodomain 2) This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. The encoded protein acts as a transcription factor and regulates procollagen lysyl hydroxylase gene expression. This protein plays a role in the terminal differentiation of somatotroph and lactotroph cell phenotypes, is involved in the development of the eye, tooth and abdominal organs, and acts as a transcriptional regulator involved in basal and hormone-regulated activity of prolactin. Mutations in this gene are associated with Axenfeld-Rieger syndrome, iridogoniodysgenesis syndrome, and sporadic cases of Peters anomaly. A similar protein in other vertebrates is involved in the determination of left-right asymmetry during development. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BS2
High AC in GnomAdExome4 at 5 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PITX2 | NM_000325.6 | c.916G>T | p.Val306Leu | missense_variant | Exon 3 of 3 | ENST00000644743.1 | NP_000316.2 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461856Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727228
GnomAD4 exome
AF:
AC:
5
AN:
1461856
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
727228
Gnomad4 AFR exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
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Bravo
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ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;.;T;T;.;T;T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
.;T;.;.;.;.;.;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
.;.;L;L;.;L;L;L;.
PrimateAI
Pathogenic
D
PROVEAN
Benign
.;N;.;N;N;N;.;.;.
REVEL
Uncertain
Sift
Benign
.;T;.;T;T;T;.;.;.
Sift4G
Benign
.;T;.;T;T;T;T;T;T
Polyphen
B;B;B;B;D;B;B;B;D
Vest4
0.57, 0.61, 0.55, 0.62, 0.61, 0.61, 0.55
MutPred
0.25
.;.;Gain of glycosylation at Y296 (P = 0.0135);Gain of glycosylation at Y296 (P = 0.0135);.;Gain of glycosylation at Y296 (P = 0.0135);Gain of glycosylation at Y296 (P = 0.0135);Gain of glycosylation at Y296 (P = 0.0135);.;
MVP
0.76
MPC
1.0
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