rs104894659
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_000529.2(MC2R):c.601C>T(p.Arg201Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
MC2R
NM_000529.2 stop_gained
NM_000529.2 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 9.32
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 12 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 18-13884918-G-A is Pathogenic according to our data. Variant chr18-13884918-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 3259.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MC2R | NM_000529.2 | c.601C>T | p.Arg201Ter | stop_gained | 2/2 | ENST00000327606.4 | |
MC2R | NM_001291911.1 | c.601C>T | p.Arg201Ter | stop_gained | 2/2 | ||
MC2R | XM_017025781.2 | c.601C>T | p.Arg201Ter | stop_gained | 3/3 | ||
MC2R | XM_047437537.1 | c.601C>T | p.Arg201Ter | stop_gained | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MC2R | ENST00000327606.4 | c.601C>T | p.Arg201Ter | stop_gained | 2/2 | 1 | NM_000529.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
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32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251354Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135862
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461882Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727244
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Glucocorticoid deficiency 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 1994 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A
Vest4
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at