12-53425683-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

18 publications found

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 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

AMHR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 522208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
AMHR2	NM_020547.3 link	c.622-6C>T		splice_region_variant, intron_variant	Intron 5 of 10	ENST00000257863.9	NP_065434.1	Q16671-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMHR2	ENST00000257863.9 link	c.622-6C>T		splice_region_variant, intron_variant	Intron 5 of 10	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

GnomAD2 exomes

AF:

0.170

AC:

42409

AN:

250184

AF XY:

0.169

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 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

African (AFR)

AF:

0.133

AC:

4440

AN:

33476

American (AMR)

AF:

0.203

AC:

9066

AN:

44646

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

4163

AN:

26122

East Asian (EAS)

AF:

0.195

AC:

7747

AN:

39688

South Asian (SAS)

AF:

0.155

AC:

13404

AN:

86248

European-Finnish (FIN)

AF:

0.145

AC:

7743

AN:

53352

Middle Eastern (MID)

AF:

0.117

AC:

675

AN:

5768

European-Non Finnish (NFE)

AF:

0.177

AC:

196998

AN:

1111832

Other (OTH)

AF:

0.167

AC:

10109

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

13021

26043

39064

52086

65107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7030

14060

21090

28120

35150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.164

AC:

24935

AN:

152136

Hom.:

2138

Cov.:

AF XY:

0.164

AC XY:

12193

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.139

AC:

5766

AN:

41506

American (AMR)

AF:

0.197

AC:

3006

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

475

AN:

3468

East Asian (EAS)

AF:

0.177

AC:

918

AN:

5178

South Asian (SAS)

AF:

0.152

AC:

735

AN:

4824

European-Finnish (FIN)

AF:

0.145

AC:

1541

AN:

10598

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.176

AC:

11980

AN:

67966

Other (OTH)

AF:

0.147

AC:

310

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1076

2152

3229

4305

5381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.169

Hom.:

3376

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

Mar 12, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Persistent Mullerian duct syndrome

Benign:2

Nov 16, 2016

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 31, 2017

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.2

(source)

DANN

Benign

0.65

PhyloP100

0.48

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over