Genetic Variant AMHR2:n.1622G>C (chr12-53430724-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000552233.5(AMHR2):n.1622G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0509 in 348,406 control chromosomes in the GnomAD database, including 2,790 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.098 ( 2400 hom., cov: 32)

Exomes 𝑓: 0.014 ( 390 hom. )

Consequence

AMHR2
ENST00000552233.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.30

Publications

9 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMHR2	NM_020547.3 link	c.1425+442G>C		intron_variant	Intron 10 of 10	ENST00000257863.9	NP_065434.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
AMHR2	ENST00000552233.5 link	n.1622G>C	non_coding_transcript_exon_variant	Exon 4 of 4	1
AMHR2	ENST00000257863.9 link	c.1425+442G>C	intron_variant	Intron 10 of 10	1	NM_020547.3	ENSP00000257863.3
AMHR2	ENST00000379791.7 link	c.1141-453G>C	intron_variant	Intron 8 of 8	1		ENSP00000369117.3
AMHR2	ENST00000550311.5 link	c.1421+442G>C	intron_variant	Intron 10 of 10	1		ENSP00000446661.1

Frequencies

GnomAD3 genomes

AF:

0.0981

AC:

14924

AN:

152118

Hom.:

2396

Cov.:

show subpopulations

Gnomad AFR

AF:

0.338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0408

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00203

Gnomad OTH

AF:

0.0684

GnomAD4 exome

AF:

0.0141

AC:

2773

AN:

196170

Hom.:

390

Cov.:

AF XY:

0.0115

AC XY:

1201

AN XY:

104306

show subpopulations

African (AFR)

AF:

0.343

AC:

2128

AN:

6200

American (AMR)

AF:

0.0245

AC:

214

AN:

8728

Ashkenazi Jewish (ASJ)

AF:

0.00361

AC:

AN:

5264

East Asian (EAS)

AF:

0.00

AC:

AN:

9256

South Asian (SAS)

AF:

0.00100

AC:

AN:

30948

European-Finnish (FIN)

AF:

0.000318

AC:

AN:

9446

Middle Eastern (MID)

AF:

0.0251

AC:

AN:

756

European-Non Finnish (NFE)

AF:

0.00137

AC:

158

AN:

115344

Other (OTH)

AF:

0.0197

AC:

201

AN:

10228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

101

202

303

404

505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<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:

0.0983

AC:

14962

AN:

152236

Hom.:

2400

Cov.:

AF XY:

0.0952

AC XY:

7091

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.338

AC:

14024

AN:

41468

American (AMR)

AF:

0.0408

AC:

624

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00165

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00203

AC:

138

AN:

68028

Other (OTH)

AF:

0.0677

AC:

143

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

506

1012

1518

2024

2530

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<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:

0.0199

Hom.:

Bravo

AF:

0.112

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

8.5

(source)

DANN

Benign

0.84

PhyloP100

2.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

Computational scores

Splicing

Publications

Other links and lift over