Variant 22-29695156-T-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 ENST00000338641.10(NF2):c.*354T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 457,612 control chromosomes in the GnomAD database, including 15,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4495 hom., cov: 33)

Exomes 𝑓: 0.25 ( 10705 hom. )

Consequence

NF2
ENST00000338641.10 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.12

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=-0.91).

BP6

Variant 22-29695156-T-C is Benign according to our data. Variant chr22-29695156-T-C is described in ClinVar as [Benign]. Clinvar id is 341085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NF2	NM_000268.4 linkuse as main transcript	c.*354T>C		3_prime_UTR_variant	16/16	ENST00000338641.10	NP_000259.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NF2	ENST00000338641.10 linkuse as main transcript	c.*354T>C		3_prime_UTR_variant	16/16	1	NM_000268.4	ENSP00000344666	P1	P35240-1

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35939

AN:

152008

Hom.:

4495

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.170

Gnomad EAS

AF:

0.439

Gnomad SAS

AF:

0.261

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.220

GnomAD4 exome

AF:

0.254

AC:

77442

AN:

305486

Hom.:

10705

Cov.:

AF XY:

0.254

AC XY:

40310

AN XY:

158748

show subpopulations

Gnomad4 AFR exome

AF:

0.215

Gnomad4 AMR exome

AF:

0.224

Gnomad4 ASJ exome

AF:

0.165

Gnomad4 EAS exome

AF:

0.456

Gnomad4 SAS exome

AF:

0.257

Gnomad4 FIN exome

AF:

0.294

Gnomad4 NFE exome

AF:

0.238

Gnomad4 OTH exome

AF:

0.237

GnomAD4 genome

AF:

0.236

AC:

35961

AN:

152126

Hom.:

4495

Cov.:

AF XY:

0.240

AC XY:

17844

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.216

Gnomad4 AMR

AF:

0.192

Gnomad4 ASJ

AF:

0.170

Gnomad4 EAS

AF:

0.439

Gnomad4 SAS

AF:

0.260

Gnomad4 FIN

AF:

0.292

Gnomad4 NFE

AF:

0.238

Gnomad4 OTH

AF:

0.218

Alfa

AF:

0.228

Hom.:

3914

Bravo

AF:

0.232

Asia WGS

AF:

0.320

AC:

1111

AN:

3478

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

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Neurofibromatosis, type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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

-0.91

CADD

Benign

0.45

DANN

Benign

0.34

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

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