12-53424172-C-A

Position:

• chr12-53424172-C-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
AMHR2	NM_020547.3	c.50-116C>A		intron_variant		ENST00000257863.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMHR2	ENST00000257863.9	c.50-116C>A		intron_variant		1	NM_020547.3	P1
AMHR2	ENST00000379791.7	c.50-116C>A		intron_variant		1
AMHR2	ENST00000550311.5	c.50-116C>A		intron_variant		1

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

Gnomad4 AFR exome AF: 0.490

Gnomad4 AMR exome AF: 0.0306

Gnomad4 ASJ exome AF: 0.00419

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00112

Gnomad4 FIN exome AF: 0.000285

Gnomad4 NFE exome AF: 0.00157

Gnomad4 OTH exome AF: 0.0331

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

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.0545

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00244

Gnomad4 OTH AF: 0.0912

Alfa AF: 0.0188 Hom.: 1121

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2019

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs784894; hg19: chr12-53817956;