12-53430724-G-C

Position:

• chr12-53430724-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020547.3(AMHR2):​c.1425+442G>C variant causes a intron 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 NM_020547.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
AMHR2	NM_020547.3	c.1425+442G>C		intron_variant		ENST00000257863.9	NP_065434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMHR2	ENST00000257863.9	c.1425+442G>C		intron_variant		1	NM_020547.3	ENSP00000257863.3
AMHR2	ENST00000379791.7	c.1141-453G>C		intron_variant		1		ENSP00000369117.3
AMHR2	ENST00000550311.5	c.1421+442G>C		intron_variant		1		ENSP00000446661.1
AMHR2	ENST00000552233.5	n.1622G>C		non_coding_transcript_exon_variant	4/4	1

Frequencies

GnomAD3 genomes AF: 0.0981 AC: 14924 AN: 152118 Hom.: 2396 Cov.: 32

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.: 0 AF XY: 0.0115 AC XY: 1201 AN XY: 104306

Gnomad4 AFR exome AF: 0.343

Gnomad4 AMR exome AF: 0.0245

Gnomad4 ASJ exome AF: 0.00361

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00100

Gnomad4 FIN exome AF: 0.000318

Gnomad4 NFE exome AF: 0.00137

Gnomad4 OTH exome AF: 0.0197

GnomAD4 genome AF: 0.0983 AC: 14962 AN: 152236 Hom.: 2400 Cov.: 32 AF XY: 0.0952 AC XY: 7091 AN XY: 74454

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.0408

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00165

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00203

Gnomad4 OTH AF: 0.0677

Alfa AF: 0.0199 Hom.: 43

Bravo AF: 0.112

Asia WGS AF: 0.0210 AC: 73 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
DANN	Benign	0.84

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

LitVar

Other links and lift over

dbSNP: rs784888; hg19: chr12-53824508;