Variant 22-29603889-G-C details in Genebe, Genetics Data Aggregator

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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

NF2 links:

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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
NF2	NM_000268.4 linkuse as main transcript	c.-110G>C		5_prime_UTR_variant	1/16	ENST00000338641.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NF2	ENST00000338641.10 linkuse as main transcript	c.-110G>C		5_prime_UTR_variant	1/16	1	NM_000268.4	P1	P35240-1

Frequencies

GnomAD3 genomes

AF:

0.870

AC:

132246

AN:

152018

Hom.:

57606

Cov.:

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.:

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.:

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2018

- -

Neurofibromatosis, type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This 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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over