12-53430724-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020547.3(AMHR2):​c.1425+442G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0509 in 348,406 control chromosomes in the GnomAD database, including 2,790 homozygotes. 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: 𝑓 0.098 (2400 hom., cov: 32)
  • Exomes 𝑓: 0.014 (390 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

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>C		intron	N/A	NP_065434.1
	AMHR2	NM_001164690.2		c.1421+442G>C		intron	N/A	NP_001158162.1
	AMHR2	NM_001164691.2		c.1141-453G>C		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>C		intron	N/A	ENSP00000257863.3
	AMHR2	ENST00000379791.7	TSL:1	c.1141-453G>C		intron	N/A	ENSP00000369117.3
	AMHR2	ENST00000550311.5	TSL:1	c.1421+442G>C		intron	N/A	ENSP00000446661.1

Frequencies

GnomAD3 genomes AF: 0.0981 AC: 14924 AN: 152118 Hom.: 2396 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0408

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00203

Gnomad OTH AF: 0.0684

GnomAD4 exome AF: 0.0141 AC: 2773 AN: 196170 Hom.: 390 Cov.: 0 AF XY: 0.0115 AC XY: 1201 AN XY: 104306

African (AFR) AF: 0.343 AC: 2128 AN: 6200

American (AMR) AF: 0.0245 AC: 214 AN: 8728

Ashkenazi Jewish (ASJ) AF: 0.00361 AC: 19 AN: 5264

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

South Asian (SAS) AF: 0.00100 AC: 31 AN: 30948

European-Finnish (FIN) AF: 0.000318 AC: 3 AN: 9446

Middle Eastern (MID) AF: 0.0251 AC: 19 AN: 756

European-Non Finnish (NFE) AF: 0.00137 AC: 158 AN: 115344

Other (OTH) AF: 0.0197 AC: 201 AN: 10228

GnomAD4 genome AF: 0.0983 AC: 14962 AN: 152236 Hom.: 2400 Cov.: 32 AF XY: 0.0952 AC XY: 7091 AN XY: 74454

African (AFR) AF: 0.338 AC: 14024 AN: 41468

American (AMR) AF: 0.0408 AC: 624 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00165 AC: 8 AN: 4834

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00203 AC: 138 AN: 68028

Other (OTH) AF: 0.0677 AC: 143 AN: 2112

Alfa AF: 0.0199 Hom.: 43

Bravo AF: 0.112

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.5
DANN	Benign	0.84
PhyloP100		2.3
Mutation Taster		=100/0	polymorphism (auto)

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;