rs142459414

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000268.4(NF2):​c.1113C>A​(p.Asn371Lys) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N371N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

NF2
NM_000268.4 missense

Scores

1
9
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.50
Variant links:
Genes affected
NF2 (HGNC:7773): (NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor) This gene encodes a protein that is similar to some members of the ERM (ezrin, radixin, moesin) family of proteins that link cytoskeletal components with proteins in the cell membrane. The encoded protein is involved in regulation of contact-dependent inhibition of cell proliferation and functions in cell-cell adhesion and transmembrane signaling. The encoded protein has been shown to interact with cell-surface proteins, proteins involved in cytoskeletal dynamics, and proteins involved in regulating ion transport. Disruption of this protein's function has been implicated in tumorigenesis and metastasis. Mutations in this gene are associated with neurofibromatosis type II which is characterized by nervous system and skin tumors and ocular abnormalities. [provided by RefSeq, May 2022]

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ACMG classification

Classification made for transcript

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=0.23443463).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NF2NM_000268.4 linkuse as main transcriptc.1113C>A p.Asn371Lys missense_variant 11/16 ENST00000338641.10 NP_000259.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NF2ENST00000338641.10 linkuse as main transcriptc.1113C>A p.Asn371Lys missense_variant 11/161 NM_000268.4 ENSP00000344666 P1P35240-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.61
BayesDel_addAF
Benign
-0.056
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
7.0
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.75
D;.;.;.;.;.;.;.;.
Eigen
Benign
-0.65
Eigen_PC
Benign
-0.82
FATHMM_MKL
Benign
0.26
N
LIST_S2
Uncertain
0.94
D;D;D;.;.;D;.;D;D
M_CAP
Uncertain
0.18
D
MetaRNN
Benign
0.23
T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
0.0033
D
MutationAssessor
Uncertain
2.5
M;.;.;M;.;.;M;.;M
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
0.72
T
PROVEAN
Uncertain
-2.7
D;N;D;D;D;D;D;D;D
REVEL
Uncertain
0.46
Sift
Benign
0.17
T;T;T;T;T;T;T;T;T
Sift4G
Benign
0.74
T;T;T;T;T;T;T;T;T
Polyphen
0.90
P;P;B;P;D;D;P;D;P
Vest4
0.48
MutPred
0.51
Gain of ubiquitination at N371 (P = 0.0022);.;.;Gain of ubiquitination at N371 (P = 0.0022);.;.;Gain of ubiquitination at N371 (P = 0.0022);.;Gain of ubiquitination at N371 (P = 0.0022);
MVP
0.82
MPC
1.7
ClinPred
0.95
D
GERP RS
-6.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.29
gMVP
0.53

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: chr22-30067928; API