12-53424714-C-T
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_020547.3(AMHR2):c.238C>T(p.Arg80Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
AMHR2
NM_020547.3 stop_gained
NM_020547.3 stop_gained
Scores
3
2
2
Clinical Significance
Conservation
PhyloP100: 1.41
Genes affected
AMHR2 (HGNC:465): (anti-Mullerian hormone receptor type 2) This gene encodes the receptor for the anti-Mullerian hormone (AMH) which, in addition to testosterone, results in male sex differentiation. AMH and testosterone are produced in the testes by different cells and have different effects. Testosterone promotes the development of male genitalia while the binding of AMH to the encoded receptor prevents the development of the mullerian ducts into uterus and Fallopian tubes. Mutations in this gene are associated with persistent Mullerian duct syndrome type II. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 12-53424714-C-T is Pathogenic according to our data. Variant chr12-53424714-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 1705324.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AMHR2 | NM_020547.3 | c.238C>T | p.Arg80Ter | stop_gained | 3/11 | ENST00000257863.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AMHR2 | ENST00000257863.9 | c.238C>T | p.Arg80Ter | stop_gained | 3/11 | 1 | NM_020547.3 | P1 | |
AMHR2 | ENST00000379791.7 | c.238C>T | p.Arg80Ter | stop_gained | 3/9 | 1 | |||
AMHR2 | ENST00000550311.5 | c.238C>T | p.Arg80Ter | stop_gained | 3/11 | 1 | |||
AMHR2 | ENST00000553037.1 | n.199C>T | non_coding_transcript_exon_variant | 2/2 | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152086Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250648Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135466
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461424Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 726982
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 152086Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74274
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Persistent Mullerian duct syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | 3billion | Sep 01, 2022 | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). Stop-gained (nonsense) is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported to be associated with AMHR2-related disorder (PMID: 8872466). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
MutationTaster
Benign
A;A;A
Vest4
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at