chr12-53424172-C-A

Variant names:

• chr12-53424172-C-A
• rs784894
• NM_020547.3:c.50-116C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_020547.3(AMHR2):​c.50-116C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0278 in 1,453,498 control chromosomes in the GnomAD database, including 8,558 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (4719 hom., cov: 32)
  • Exomes 𝑓: 0.015 (3839 hom.)
• Consequence: AMHR2 NM_020547.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.20
• Publications: 7 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=-0.42).
• BP6: Variant 12-53424172-C-A is Benign according to our data. Variant chr12-53424172-C-A is described in ClinVar as [Benign]. Clinvar id is 1280959.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMHR2	NM_020547.3	c.50-116C>A		intron_variant	Intron 1 of 10	ENST00000257863.9	NP_065434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMHR2	ENST00000257863.9	c.50-116C>A		intron_variant	Intron 1 of 10	1	NM_020547.3	ENSP00000257863.3
AMHR2	ENST00000379791.7	c.50-116C>A		intron_variant	Intron 1 of 8	1		ENSP00000369117.3
AMHR2	ENST00000550311.5	c.50-116C>A		intron_variant	Intron 1 of 10	1		ENSP00000446661.1
AMHR2	ENST00000553037.1	n.-106C>A		upstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20568 AN: 152080 Hom.: 4692 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0545

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00244

Gnomad OTH AF: 0.0922

GnomAD4 exome AF: 0.0152 AC: 19788 AN: 1301300 Hom.: 3839 Cov.: 20 AF XY: 0.0131 AC XY: 8540 AN XY: 654298

African (AFR) AF: 0.490 AC: 14755 AN: 30100

American (AMR) AF: 0.0306 AC: 1344 AN: 43944

Ashkenazi Jewish (ASJ) AF: 0.00419 AC: 103 AN: 24580

East Asian (EAS) AF: 0.00 AC: 0 AN: 38872

South Asian (SAS) AF: 0.00112 AC: 91 AN: 81392

European-Finnish (FIN) AF: 0.000285 AC: 15 AN: 52626

Middle Eastern (MID) AF: 0.0342 AC: 139 AN: 4064

European-Non Finnish (NFE) AF: 0.00157 AC: 1525 AN: 970856

Other (OTH) AF: 0.0331 AC: 1816 AN: 54866

GnomAD4 genome AF: 0.136 AC: 20653 AN: 152198 Hom.: 4719 Cov.: 32 AF XY: 0.131 AC XY: 9754 AN XY: 74414

African (AFR) AF: 0.469 AC: 19423 AN: 41456

American (AMR) AF: 0.0545 AC: 833 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4828

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00244 AC: 166 AN: 68030

Other (OTH) AF: 0.0912 AC: 193 AN: 2116

Alfa AF: 0.0478 Hom.: 4947

Bravo AF: 0.155

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 16, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30786001) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Benign	0.73
PhyloP100		1.2
PromoterAI		-0.033	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs784894; hg19: chr12-53817956;