NM_020547.3:c.1425+442G>A

Variant names:

• chr12-53430724-G-A
• rs784888
• NM_020547.3:c.1425+442G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020547.3(AMHR2):​c.1425+442G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AMHR2 NM_020547.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30
• Publications: 9 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, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).

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.1425+442G>A		intron	N/A	NP_065434.1
	AMHR2	NM_001164690.2		c.1421+442G>A		intron	N/A	NP_001158162.1
	AMHR2	NM_001164691.2		c.1141-453G>A		intron	N/A	NP_001158163.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMHR2	ENST00000257863.9	TSL:1 MANE Select	c.1425+442G>A		intron	N/A	ENSP00000257863.3
	AMHR2	ENST00000379791.7	TSL:1	c.1141-453G>A		intron	N/A	ENSP00000369117.3
	AMHR2	ENST00000550311.5	TSL:1	c.1421+442G>A		intron	N/A	ENSP00000446661.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 196186 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 104312

African (AFR) AF: 0.00 AC: 0 AN: 6210

American (AMR) AF: 0.00 AC: 0 AN: 8728

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5264

East Asian (EAS) AF: 0.00 AC: 0 AN: 9256

South Asian (SAS) AF: 0.00 AC: 0 AN: 30948

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9446

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 115346

Other (OTH) AF: 0.00 AC: 0 AN: 10230

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 43

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.9
DANN	Benign	0.85
PhyloP100		2.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs784888; hg19: chr12-53824508;