12-53424449-C-A

Variant names:

• chr12-53424449-C-A
• rs200109472
• NM_020547.3:c.211C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_020547.3(AMHR2):​c.211C>A​(p.Arg71Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000558 in 1,613,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: AMHR2 NM_020547.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.21
• Publications: 2 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 12-53424449-C-A is Benign according to our data. Variant chr12-53424449-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 731907.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.21 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMHR2	NM_020547.3	c.211C>A	p.Arg71Arg	synonymous_variant	Exon 2 of 11	ENST00000257863.9	NP_065434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMHR2	ENST00000257863.9	c.211C>A	p.Arg71Arg	synonymous_variant	Exon 2 of 11	1	NM_020547.3	ENSP00000257863.3
AMHR2	ENST00000379791.7	c.211C>A	p.Arg71Arg	synonymous_variant	Exon 2 of 9	1		ENSP00000369117.3
AMHR2	ENST00000550311.5	c.211C>A	p.Arg71Arg	synonymous_variant	Exon 2 of 11	1		ENSP00000446661.1
AMHR2	ENST00000553037.1	n.172C>A		non_coding_transcript_exon_variant	Exon 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152128 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000240 AC: 6 AN: 249708 AF XY: 0.0000148

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000531

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000575 AC: 84 AN: 1461070 Hom.: 0 Cov.: 32 AF XY: 0.0000633 AC XY: 46 AN XY: 726780

African (AFR) AF: 0.0000299 AC: 1 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5674

European-Non Finnish (NFE) AF: 0.0000711 AC: 79 AN: 1111722

Other (OTH) AF: 0.0000663 AC: 4 AN: 60376

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152128 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74324

African (AFR) AF: 0.00 AC: 0 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000680

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	9.6
DANN	Benign	0.67
PhyloP100		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200109472; hg19: chr12-53818233;