rs104894661

Variant names:

• chr18-13885200-C-A
• NM_000529.2:c.319G>T

Your query was ambiguous. Multiple possible variants found:

• chr18-13885200-C-A
• chr18-13885200-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_000529.2(MC2R):​c.319G>T​(p.Asp107Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MC2R NM_000529.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.61

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.969

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MC2R	NM_000529.2	c.319G>T	p.Asp107Tyr	missense_variant	Exon 2 of 2	ENST00000327606.4	NP_000520.1
MC2R	NM_001291911.1	c.319G>T	p.Asp107Tyr	missense_variant	Exon 2 of 2		NP_001278840.1
MC2R	XM_017025781.2	c.319G>T	p.Asp107Tyr	missense_variant	Exon 3 of 3		XP_016881270.1
MC2R	XM_047437537.1	c.319G>T	p.Asp107Tyr	missense_variant	Exon 4 of 4		XP_047293493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MC2R	ENST00000327606.4	c.319G>T	p.Asp107Tyr	missense_variant	Exon 2 of 2	1	NM_000529.2	ENSP00000333821.2
MC2R	ENST00000399821.2	c.319G>T	p.Asp107Tyr	missense_variant	Exon 2 of 2	3		ENSP00000382718.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461880 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.71	D;.
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Uncertain	-0.084	T
MutationAssessor	Pathogenic	3.4	M;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-8.5	D;D
REVEL	Uncertain	0.46
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0010	D;.
Polyphen		1.0	D;.
Vest4		0.46
MutPred		0.83		Loss of disorder (P = 0.0888);Loss of disorder (P = 0.0888);
MVP		0.76
MPC		0.84
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.96
gMVP		0.88

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-13885199;