6-99947907-T-G

Position:

• chr6-99947907-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040179.2(MCHR2):​c.247A>C​(p.Ile83Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MCHR2 NM_001040179.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.258

Genes affected

MCHR2 (HGNC:20867): (melanin concentrating hormone receptor 2) Predicted to enable G protein-coupled peptide receptor activity. Predicted to be involved in neuropeptide signaling pathway. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.068464816).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCHR2	NM_001040179.2	c.247A>C	p.Ile83Leu	missense_variant	3/6	ENST00000281806.7	NP_001035269.1
MCHR2	NM_032503.3	c.247A>C	p.Ile83Leu	missense_variant	3/6		NP_115892.2
MCHR2	XM_024446571.2	c.247A>C	p.Ile83Leu	missense_variant	3/6		XP_024302339.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCHR2	ENST00000281806.7	c.247A>C	p.Ile83Leu	missense_variant	3/6	2	NM_001040179.2	ENSP00000281806.2
MCHR2	ENST00000369212.2	c.247A>C	p.Ile83Leu	missense_variant	3/6	1		ENSP00000358214.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2023

The c.247A>C (p.I83L) alteration is located in exon 3 (coding exon 2) of the MCHR2 gene. This alteration results from a A to C substitution at nucleotide position 247, causing the isoleucine (I) at amino acid position 83 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.67
DEOGEN2	Benign	0.072	T;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.66	T;.
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.068	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.77	N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.83	N;N
REVEL	Benign	0.089
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.025	B;B
Vest4		0.30
MutPred		0.42		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP		0.40
MPC		0.18
ClinPred		0.39	T
GERP RS		4.6
Varity_R		0.14
gMVP		0.20

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: chr6-100395783;