chr22-29603889-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000268.4(NF2):​c.-110G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 826,994 control chromosomes in the GnomAD database, including 317,277 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 57656 hom., cov: 35)
Exomes 𝑓: 0.88 ( 259621 hom. )

Consequence

NF2
NM_000268.4 5_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.279
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 Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 22-29603889-G-C is Benign according to our data. Variant chr22-29603889-G-C is described in ClinVar as [Benign]. Clinvar id is 341066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NF2NM_000268.4 linkuse as main transcriptc.-110G>C 5_prime_UTR_variant 1/16 ENST00000338641.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NF2ENST00000338641.10 linkuse as main transcriptc.-110G>C 5_prime_UTR_variant 1/161 NM_000268.4 P1P35240-1

Frequencies

GnomAD3 genomes
AF:
0.870
AC:
132246
AN:
152018
Hom.:
57606
Cov.:
35
show subpopulations
Gnomad AFR
AF:
0.849
Gnomad AMI
AF:
0.851
Gnomad AMR
AF:
0.898
Gnomad ASJ
AF:
0.903
Gnomad EAS
AF:
0.946
Gnomad SAS
AF:
0.845
Gnomad FIN
AF:
0.856
Gnomad MID
AF:
0.904
Gnomad NFE
AF:
0.872
Gnomad OTH
AF:
0.892
GnomAD4 exome
AF:
0.877
AC:
591539
AN:
674858
Hom.:
259621
Cov.:
9
AF XY:
0.875
AC XY:
304382
AN XY:
347734
show subpopulations
Gnomad4 AFR exome
AF:
0.850
Gnomad4 AMR exome
AF:
0.882
Gnomad4 ASJ exome
AF:
0.904
Gnomad4 EAS exome
AF:
0.963
Gnomad4 SAS exome
AF:
0.841
Gnomad4 FIN exome
AF:
0.856
Gnomad4 NFE exome
AF:
0.876
Gnomad4 OTH exome
AF:
0.877
GnomAD4 genome
AF:
0.870
AC:
132354
AN:
152136
Hom.:
57656
Cov.:
35
AF XY:
0.869
AC XY:
64621
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.849
Gnomad4 AMR
AF:
0.898
Gnomad4 ASJ
AF:
0.903
Gnomad4 EAS
AF:
0.947
Gnomad4 SAS
AF:
0.846
Gnomad4 FIN
AF:
0.856
Gnomad4 NFE
AF:
0.872
Gnomad4 OTH
AF:
0.893
Alfa
AF:
0.867
Hom.:
7099
Bravo
AF:
0.872
Asia WGS
AF:
0.890
AC:
3093
AN:
3476

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJun 24, 2018- -
Neurofibromatosis, type 2 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.68
CADD
Benign
13
DANN
Benign
0.89

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1800540; hg19: chr22-29999878; API