Variant chr12-53425683-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020547.3(AMHR2):c.622-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,613,642 control chromosomes in the GnomAD database, including 24,721 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2138 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22583 hom. )

Consequence

AMHR2
NM_020547.3 splice_region, intron

Scores

Splicing: ADA: 0.0001164

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.480

Variant links:

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 links:

AMHR2 (HGNC:):

AMHR2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 12-53425683-C-T is Benign according to our data. Variant chr12-53425683-C-T is described in ClinVar as [Benign]. Clinvar id is 522208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-53425683-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMHR2	NM_020547.3 linkuse as main transcript	c.622-6C>T		splice_region_variant, intron_variant		ENST00000257863.9	NP_065434.1	Q16671-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMHR2	ENST00000257863.9 linkuse as main transcript	c.622-6C>T		splice_region_variant, intron_variant		1	NM_020547.3	ENSP00000257863.3		Q16671-1

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

24920

AN:

152018

Hom.:

2134

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.184

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.152

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.176

Gnomad OTH

AF:

0.149

GnomAD3 exomes

AF:

0.170

AC:

42409

AN:

250184

Hom.:

3611

AF XY:

0.169

AC XY:

22839

AN XY:

135292

show subpopulations

Gnomad AFR exome

AF:

0.138

Gnomad AMR exome

AF:

0.198

Gnomad ASJ exome

AF:

0.161

Gnomad EAS exome

AF:

0.170

Gnomad SAS exome

AF:

0.155

Gnomad FIN exome

AF:

0.143

Gnomad NFE exome

AF:

0.175

Gnomad OTH exome

AF:

0.164

GnomAD4 exome

AF:

0.174

AC:

254345

AN:

1461506

Hom.:

22583

Cov.:

AF XY:

0.173

AC XY:

125833

AN XY:

727024

show subpopulations

Gnomad4 AFR exome

AF:

0.133

Gnomad4 AMR exome

AF:

0.203

Gnomad4 ASJ exome

AF:

0.159

Gnomad4 EAS exome

AF:

0.195

Gnomad4 SAS exome

AF:

0.155

Gnomad4 FIN exome

AF:

0.145

Gnomad4 NFE exome

AF:

0.177

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.164

AC:

24935

AN:

152136

Hom.:

2138

Cov.:

AF XY:

0.164

AC XY:

12193

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.139

Gnomad4 AMR

AF:

0.197

Gnomad4 ASJ

AF:

0.137

Gnomad4 EAS

AF:

0.177

Gnomad4 SAS

AF:

0.152

Gnomad4 FIN

AF:

0.145

Gnomad4 NFE

AF:

0.176

Gnomad4 OTH

AF:

0.147

Alfa

AF:

0.170

Hom.:

2751

Bravo

AF:

0.164

Asia WGS

AF:

0.145

AC:

503

AN:

3478

EpiCase

AF:

0.175

EpiControl

AF:

0.172

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 12, 2019	- -

Persistent Mullerian duct syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	May 31, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Nov 16, 2016	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.2

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over