Variant 22-29642163-A-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.364-39A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,528,952 control chromosomes in the GnomAD database, including 28,938 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2387 hom., cov: 32)

Exomes 𝑓: 0.18 ( 26551 hom. )

Consequence

NF2
NM_000268.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.64

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:

NF2 (HGNC:):

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=-0.86).

BP6

Variant 22-29642163-A-C is Benign according to our data. Variant chr22-29642163-A-C is described in ClinVar as [Benign]. Clinvar id is 262993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.55 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.364-39A>C		intron_variant		ENST00000338641.10	NP_000259.1	P35240-1A0A024R1J8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NF2	ENST00000338641.10 linkuse as main transcript	c.364-39A>C		intron_variant		1	NM_000268.4	ENSP00000344666.5		P35240-1

Frequencies

GnomAD3 genomes

AF:

0.149

AC:

22627

AN:

152034

Hom.:

2393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0418

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.182

Gnomad ASJ

AF:

0.233

Gnomad EAS

AF:

0.567

Gnomad SAS

AF:

0.139

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.194

Gnomad NFE

AF:

0.172

Gnomad OTH

AF:

0.170

GnomAD3 exomes

AF:

0.194

AC:

48368

AN:

249720

Hom.:

6448

AF XY:

0.190

AC XY:

25702

AN XY:

134978

show subpopulations

Gnomad AFR exome

AF:

0.0393

Gnomad AMR exome

AF:

0.207

Gnomad ASJ exome

AF:

0.227

Gnomad EAS exome

AF:

0.586

Gnomad SAS exome

AF:

0.127

Gnomad FIN exome

AF:

0.143

Gnomad NFE exome

AF:

0.173

Gnomad OTH exome

AF:

0.187

GnomAD4 exome

AF:

0.181

AC:

249605

AN:

1376798

Hom.:

26551

Cov.:

AF XY:

0.179

AC XY:

123719

AN XY:

689934

show subpopulations

Gnomad4 AFR exome

AF:

0.0367

Gnomad4 AMR exome

AF:

0.203

Gnomad4 ASJ exome

AF:

0.224

Gnomad4 EAS exome

AF:

0.553

Gnomad4 SAS exome

AF:

0.126

Gnomad4 FIN exome

AF:

0.143

Gnomad4 NFE exome

AF:

0.176

Gnomad4 OTH exome

AF:

0.187

GnomAD4 genome

AF:

0.149

AC:

22615

AN:

152154

Hom.:

2387

Cov.:

AF XY:

0.149

AC XY:

11097

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0418

Gnomad4 AMR

AF:

0.182

Gnomad4 ASJ

AF:

0.233

Gnomad4 EAS

AF:

0.567

Gnomad4 SAS

AF:

0.139

Gnomad4 FIN

AF:

0.137

Gnomad4 NFE

AF:

0.172

Gnomad4 OTH

AF:

0.167

Alfa

AF:

0.162

Hom.:

1161

Bravo

AF:

0.154

Asia WGS

AF:

0.287

AC:

997

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Neurofibromatosis, type 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.036

DANN

Benign

0.49

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