12-53425683-C-T

Variant names:

• chr12-53425683-C-T
• rs2071558
• NM_020547.3:c.622-6C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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

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, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020547.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMHR2	NM_020547.3	MANE Select	c.622-6C>T		splice_region intron	N/A	NP_065434.1	Q16671-1
	AMHR2	NM_001164690.2		c.622-6C>T		splice_region intron	N/A	NP_001158162.1	Q16671-2
	AMHR2	NM_001164691.2		c.622-6C>T		splice_region intron	N/A	NP_001158163.1	Q16671-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMHR2	ENST00000257863.9	TSL:1 MANE Select	c.622-6C>T		splice_region intron	N/A	ENSP00000257863.3	Q16671-1
	AMHR2	ENST00000379791.7	TSL:1	c.622-6C>T		splice_region intron	N/A	ENSP00000369117.3	Q16671-3
	AMHR2	ENST00000550311.5	TSL:1	c.622-6C>T		splice_region intron	N/A	ENSP00000446661.1	Q16671-2

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24920 AN: 152018 Hom.: 2134 Cov.: 32

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

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.: 34 AF XY: 0.173 AC XY: 125833 AN XY: 727024

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

GnomAD4 genome AF: 0.164 AC: 24935 AN: 152136 Hom.: 2138 Cov.: 32 AF XY: 0.164 AC XY: 12193 AN XY: 74378

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: 36 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11980 AN: 67966

Other (OTH) AF: 0.147 AC: 310 AN: 2112

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Persistent Mullerian duct syndrome (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.2
DANN	Benign	0.65
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2071558; hg19: chr12-53819467; COSMIC: COSV57687524; COSMIC: COSV57687524;