Genetic Variant AMHR2:p.Arg71Pro (chr12-53424450-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020547.3(AMHR2):c.212G>C(p.Arg71Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

AMHR2
NM_020547.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.34

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19740888).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMHR2	NM_020547.3 link	c.212G>C	p.Arg71Pro	missense_variant	Exon 2 of 11	ENST00000257863.9	NP_065434.1	Q16671-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AMHR2	ENST00000257863.9 link	c.212G>C	p.Arg71Pro	missense_variant	Exon 2 of 11	1	NM_020547.3	ENSP00000257863.3	Q16671-1
AMHR2	ENST00000379791.7 link	c.212G>C	p.Arg71Pro	missense_variant	Exon 2 of 9	1		ENSP00000369117.3	Q16671-3
AMHR2	ENST00000550311.5 link	c.212G>C	p.Arg71Pro	missense_variant	Exon 2 of 11	1		ENSP00000446661.1	Q16671-2
AMHR2	ENST00000553037.1 link	n.173G>C		non_coding_transcript_exon_variant	Exon 1 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249466

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134888

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460988

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726732

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Uncertain

0.068

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Uncertain

0.74

D;.;.

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.77

T;T;T

M_CAP

Benign

0.049

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Uncertain

0.24

MutationAssessor

Benign

0.69

N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.8

N;N;N

REVEL

Uncertain

0.38

Sift

Benign

0.13

T;T;T

Sift4G

Uncertain

0.051

T;D;D

Polyphen

0.52

P;.;.

Vest4

0.49

MutPred

0.50

Gain of catalytic residue at Q73 (P = 0.0183);Gain of catalytic residue at Q73 (P = 0.0183);Gain of catalytic residue at Q73 (P = 0.0183);

MVP

0.85

MPC

0.15

ClinPred

0.063

GERP RS

-2.4

Varity_R

0.69

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over