Variant chr22-29603754-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000268.4(NF2):c.-245C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00263 in 518,432 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 2 hom. )

Consequence

NF2
NM_000268.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.149

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 22-29603754-C-G is Benign according to our data. Variant chr22-29603754-C-G is described in ClinVar as [Benign]. Clinvar id is 341064.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00232 (353/152292) while in subpopulation NFE AF= 0.004 (272/68004). AF 95% confidence interval is 0.00361. There are 0 homozygotes in gnomad4. There are 180 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 353 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NF2	NM_000268.4 linkuse as main transcript	c.-245C>G		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.-245C>G		5_prime_UTR_variant	1/16	1	NM_000268.4	P1	P35240-1

Frequencies

GnomAD3 genomes

AF:

0.00232

AC:

353

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00263

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00400

Gnomad OTH

AF:

0.00239

GnomAD4 exome

AF:

0.00277

AC:

1013

AN:

366140

Hom.:

Cov.:

AF XY:

0.00263

AC XY:

502

AN XY:

190754

show subpopulations

Gnomad4 AFR exome

AF:

0.000629

Gnomad4 AMR exome

AF:

0.00138

Gnomad4 ASJ exome

AF:

0.000351

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000345

Gnomad4 FIN exome

AF:

0.00101

Gnomad4 NFE exome

AF:

0.00396

Gnomad4 OTH exome

AF:

0.00243

GnomAD4 genome

AF:

0.00232

AC:

353

AN:

152292

Hom.:

Cov.:

AF XY:

0.00242

AC XY:

180

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00263

Gnomad4 NFE

AF:

0.00400

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00122

Hom.:

Bravo

AF:

0.00212

Asia WGS

AF:

0.000289

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

-0.83

CADD

Benign

3.8

DANN

Benign

0.56

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