20-64105952-C-T

Variant names:

• chr20-64105952-C-T
• NM_005286.4:c.880G>A

Variant summary

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

The NM_005286.4(NPBWR2):​c.880G>A​(p.Val294Ile) 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: 30)
• Consequence: NPBWR2 NM_005286.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.31

Genes affected

NPBWR2 (HGNC:4530): (neuropeptides B and W receptor 2) The protein encoded by this gene is an integral membrane protein and G protein-coupled receptor. The encoded protein is similar in sequence to another G protein-coupled receptor (GPR7), and it is structurally similar to opioid and somatostatin receptors. This protein binds neuropeptides B and W. This gene is intronless and is expressed primarily in the frontal cortex of the brain. [provided by RefSeq, Jul 2008]

MYT1 (HGNC:7622): (myelin transcription factor 1) The protein encoded by this gene is a member of a family of neural specific, zinc finger-containing DNA-binding proteins. The protein binds to the promoter regions of proteolipid proteins of the central nervous system and plays a role in the developing nervous system. [provided by RefSeq, Jul 2008]

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=0.1276052).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPBWR2	NM_005286.4	c.880G>A	p.Val294Ile	missense_variant	Exon 2 of 2	ENST00000684052.1	NP_005277.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPBWR2	ENST00000684052.1	c.880G>A	p.Val294Ile	missense_variant	Exon 2 of 2		NM_005286.4	ENSP00000508236.1
NPBWR2	ENST00000369768.1	c.880G>A	p.Val294Ile	missense_variant	Exon 1 of 1	6		ENSP00000358783.1
MYT1	ENST00000659024.1	c.-313+3397C>T		intron_variant	Intron 1 of 16			ENSP00000499493.1
MYT1	ENST00000644172.2	c.22+3397C>T		intron_variant	Intron 1 of 2			ENSP00000493561.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.880G>A (p.V294I) alteration is located in exon 1 (coding exon 1) of the NPBWR2 gene. This alteration results from a G to A substitution at nucleotide position 880, causing the valine (V) at amino acid position 294 to be replaced by an isoleucine (I). 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	0.10
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.50
FATHMM_MKL	Uncertain	0.88	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.033
Sift	Benign	0.81	T
Sift4G	Benign	0.46	T
Polyphen		0.13	B
Vest4		0.15
MutPred		0.32		Loss of catalytic residue at V294 (P = 0.0243);
MVP		0.50
MPC		0.49
ClinPred		0.66	D
GERP RS		3.3
Varity_R		0.13
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr20-62737305;