12-53423453-A-G

Variant names:

• chr12-53423453-A-G
• rs2002555
• ENST00000963564.1:c.-482A>G

Variant summary

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

The ENST00000963564.1(AMHR2):​c.-482A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,180 control chromosomes in the GnomAD database, including 2,050 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 0.16 (2050 hom., cov: 32)
• Consequence: AMHR2 ENST00000963564.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 54 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000963564.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMHR2	ENST00000963564.1		c.-482A>G		upstream_gene	N/A	ENSP00000633623.1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24402 AN: 152064 Hom.: 2046 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.160 AC: 24416 AN: 152180 Hom.: 2050 Cov.: 32 AF XY: 0.161 AC XY: 11942 AN XY: 74400

African (AFR) AF: 0.128 AC: 5317 AN: 41540

American (AMR) AF: 0.196 AC: 2987 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3468

East Asian (EAS) AF: 0.171 AC: 884 AN: 5170

South Asian (SAS) AF: 0.151 AC: 728 AN: 4828

European-Finnish (FIN) AF: 0.146 AC: 1547 AN: 10590

Middle Eastern (MID) AF: 0.123 AC: 36 AN: 292

European-Non Finnish (NFE) AF: 0.176 AC: 11968 AN: 68000

Other (OTH) AF: 0.144 AC: 304 AN: 2110

Alfa AF: 0.168 Hom.: 2735

Bravo AF: 0.160

Asia WGS AF: 0.147 AC: 509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.5
DANN	Benign	0.60
PhyloP100		1.1
PromoterAI		-0.0072	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2002555; hg19: chr12-53817237;