chr18-13882487-C-A

Position:

• chr18-13882487-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000529.2(MC2R):​c.*2138G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,244 control chromosomes in the GnomAD database, including 1,904 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1904 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MC2R NM_000529.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.372

Genes affected

MC2R (HGNC:6930): (melanocortin 2 receptor) MC2R encodes one member of the five-member G-protein associated melanocortin receptor family. Melanocortins (melanocyte-stimulating hormones and adrenocorticotropic hormone) are peptides derived from pro-opiomelanocortin (POMC). MC2R is selectively activated by adrenocorticotropic hormone, whereas the other four melanocortin receptors recognize a variety of melanocortin ligands. Mutations in MC2R can result in familial glucocorticoid deficiency. Alternate transcript variants have been found for this gene. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 18-13882487-C-A is Benign according to our data. Variant chr18-13882487-C-A is described in ClinVar as [Benign]. Clinvar id is 326128.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MC2R	NM_000529.2	c.*2138G>T		3_prime_UTR_variant	2/2	ENST00000327606.4
MC2R	NM_001291911.1	c.*2138G>T		3_prime_UTR_variant	2/2
MC2R	XM_017025781.2	c.*2138G>T		3_prime_UTR_variant	3/3
MC2R	XM_047437537.1	c.*2138G>T		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MC2R	ENST00000327606.4	c.*2138G>T		3_prime_UTR_variant	2/2	1	NM_000529.2	P1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17712 AN: 152126 Hom.: 1897 Cov.: 33

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0473

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.0784

Gnomad FIN AF: 0.0184

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0334

Gnomad OTH AF: 0.0905

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.117 AC: 17759 AN: 152244 Hom.: 1904 Cov.: 33 AF XY: 0.117 AC XY: 8701 AN XY: 74442

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.0473

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.0785

Gnomad4 FIN AF: 0.0184

Gnomad4 NFE AF: 0.0335

Gnomad4 OTH AF: 0.0910

Alfa AF: 0.0461 Hom.: 402

Bravo AF: 0.131

Asia WGS AF: 0.143 AC: 494 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Glucocorticoid deficiency 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.73
DANN	Benign	0.53

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: rs3744819; hg19: chr18-13882486;