12-53424132-T-A

Variant names:

• chr12-53424132-T-A
• rs2272002
• NM_020547.3:c.49+149T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020547.3(AMHR2):​c.49+149T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,305,880 control chromosomes in the GnomAD database, including 13,239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1168 hom., cov: 32)
  • Exomes 𝑓: 0.14 (12071 hom.)
• Consequence: AMHR2 NM_020547.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0300
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 12-53424132-T-A is Benign according to our data. Variant chr12-53424132-T-A is described in ClinVar as [Benign]. Clinvar id is 1233614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMHR2	NM_020547.3	c.49+149T>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.49+149T>A		intron_variant	Intron 1 of 10	1	NM_020547.3	ENSP00000257863.3
AMHR2	ENST00000379791.7	c.49+149T>A		intron_variant	Intron 1 of 8	1		ENSP00000369117.3
AMHR2	ENST00000550311.5	c.49+149T>A		intron_variant	Intron 1 of 10	1		ENSP00000446661.1
AMHR2	ENST00000553037.1	n.-146T>A		upstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17276 AN: 152146 Hom.: 1168 Cov.: 32

Gnomad AFR AF: 0.0576

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0853

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0476

Gnomad SAS AF: 0.0675

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.138 AC: 159595 AN: 1153616 Hom.: 12071 Cov.: 16 AF XY: 0.137 AC XY: 79823 AN XY: 583602

African (AFR) AF: 0.0522 AC: 1423 AN: 27278

American (AMR) AF: 0.0695 AC: 2851 AN: 41038

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 3239 AN: 22706

East Asian (EAS) AF: 0.0603 AC: 2275 AN: 37742

South Asian (SAS) AF: 0.0735 AC: 5567 AN: 75764

European-Finnish (FIN) AF: 0.129 AC: 6566 AN: 51024

Middle Eastern (MID) AF: 0.0876 AC: 381 AN: 4348

European-Non Finnish (NFE) AF: 0.155 AC: 130896 AN: 843764

Other (OTH) AF: 0.128 AC: 6397 AN: 49952

GnomAD4 genome AF: 0.113 AC: 17272 AN: 152264 Hom.: 1168 Cov.: 32 AF XY: 0.111 AC XY: 8244 AN XY: 74442

African (AFR) AF: 0.0575 AC: 2390 AN: 41570

American (AMR) AF: 0.0852 AC: 1303 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 423 AN: 3470

East Asian (EAS) AF: 0.0477 AC: 247 AN: 5180

South Asian (SAS) AF: 0.0675 AC: 326 AN: 4828

European-Finnish (FIN) AF: 0.133 AC: 1407 AN: 10606

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10761 AN: 67996

Other (OTH) AF: 0.106 AC: 224 AN: 2116

Alfa AF: 0.130 Hom.: 170

Bravo AF: 0.106

Asia WGS AF: 0.0680 AC: 235 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.6
DANN	Benign	0.78
PhyloP100		-0.030
PromoterAI		-0.0082	Neutral
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: rs2272002; hg19: chr12-53817916; COSMIC: COSV57687460; COSMIC: COSV57687460;