chr12-53424315-TC-T
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_020547.3(AMHR2):c.78delC(p.Phe27LeufsTer17) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,448 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
AMHR2
NM_020547.3 frameshift
NM_020547.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.628
Publications
2 publications found
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]
AMHR2 Gene-Disease associations (from GenCC):
- persistent Mullerian duct syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 31 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 12-53424315-TC-T is Pathogenic according to our data. Variant chr12-53424315-TC-T is described in ClinVar as [Pathogenic]. Clinvar id is 3574976.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| AMHR2 | ENST00000257863.9 | c.78delC | p.Phe27LeufsTer17 | frameshift_variant | Exon 2 of 11 | 1 | NM_020547.3 | ENSP00000257863.3 | ||
| AMHR2 | ENST00000379791.7 | c.78delC | p.Phe27LeufsTer17 | frameshift_variant | Exon 2 of 9 | 1 | ENSP00000369117.3 | |||
| AMHR2 | ENST00000550311.5 | c.78delC | p.Phe27LeufsTer17 | frameshift_variant | Exon 2 of 11 | 1 | ENSP00000446661.1 | |||
| AMHR2 | ENST00000553037.1 | n.39delC | non_coding_transcript_exon_variant | Exon 1 of 2 | 4 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460448Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726506 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1460448
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
726506
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33426
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86186
European-Finnish (FIN)
AF:
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
AC:
0
AN:
4596
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111998
Other (OTH)
AF:
AC:
0
AN:
60264
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Persistent Mullerian duct syndrome Pathogenic:1
Mar 27, 2024
Fulgent Genetics, Fulgent Genetics
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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
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