12-53424293-CCA-GCG

Variant names:

• chr12-53424293-CCA-GCG
• NM_020547.3:c.55_57delCCAinsGCG
• AMHR2 p.Pro19Ala

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PS1

The NM_020547.3(AMHR2):​c.55_57delCCAinsGCG​(p.Pro19Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely pathogenic in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AMHR2 NM_020547.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• Publications: 0 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 syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PS1: Transcript NM_020547.3 (AMHR2) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020547.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMHR2	NM_020547.3	MANE Select	c.55_57delCCAinsGCG	p.Pro19Ala	missense	N/A	NP_065434.1	Q16671-1
	AMHR2	NM_001164690.2		c.55_57delCCAinsGCG	p.Pro19Ala	missense	N/A	NP_001158162.1	Q16671-2
	AMHR2	NM_001164691.2		c.55_57delCCAinsGCG	p.Pro19Ala	missense	N/A	NP_001158163.1	Q16671-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMHR2	ENST00000257863.9	TSL:1 MANE Select	c.55_57delCCAinsGCG	p.Pro19Ala	missense	N/A	ENSP00000257863.3	Q16671-1
	AMHR2	ENST00000379791.7	TSL:1	c.55_57delCCAinsGCG	p.Pro19Ala	missense	N/A	ENSP00000369117.3	Q16671-3
	AMHR2	ENST00000550311.5	TSL:1	c.55_57delCCAinsGCG	p.Pro19Ala	missense	N/A	ENSP00000446661.1	Q16671-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-53818077;