6-99955999-A-G

Position:

• chr6-99955999-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001040179.2(MCHR2):​c.149T>C​(p.Val50Ala) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MCHR2 NM_001040179.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.37

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29131386).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCHR2	NM_001040179.2	c.149T>C	p.Val50Ala	missense_variant	2/6	ENST00000281806.7	NP_001035269.1
MCHR2	NM_032503.3	c.149T>C	p.Val50Ala	missense_variant	2/6		NP_115892.2
MCHR2	XM_024446571.2	c.149T>C	p.Val50Ala	missense_variant	2/6		XP_024302339.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCHR2	ENST00000281806.7	c.149T>C	p.Val50Ala	missense_variant	2/6	2	NM_001040179.2	ENSP00000281806.2
MCHR2	ENST00000369212.2	c.149T>C	p.Val50Ala	missense_variant	2/6	1		ENSP00000358214.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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 05, 2022

The c.149T>C (p.V50A) alteration is located in exon 2 (coding exon 1) of the MCHR2 gene. This alteration results from a T to C substitution at nucleotide position 149, causing the valine (V) at amino acid position 50 to be replaced by an alanine (A). 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	0.098
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.068
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.52	T;.
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;L
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.074
Sift	Benign	0.037	D;D
Sift4G	Benign	0.088	T;T
Polyphen		0.0060	B;B
Vest4		0.25
MutPred		0.41		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP		0.57
MPC		0.076
ClinPred		0.48	T
GERP RS		4.9
Varity_R		0.22
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-100403875;