Genetic Variant MEG3:n.2309delC (chr14-100835270-GC-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The ENST00000398461.5(MEG3):n.2309delC variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00739 in 158,932 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0075 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 0 hom. )

Consequence

MEG3
ENST00000398461.5 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.218

Variant links:

Genes affected

MEG3 (HGNC:14575): (maternally expressed 3) This gene is a maternally expressed imprinted gene. Multiple alternatively spliced transcript variants have been transcribed from this gene and all of them are long non-coding RNAs (lncRNAs). This gene is expressed in many normal tissues, but its expression is lost in multiple cancer cell lines of various tissue origins. It inhibits tumor cell proliferation in vitro. It also interacts with the tumor suppressor p53, and regulates p53 target gene expression. Its deletion enhances angiogenesis in vivo. Many experimental evidences demonstrate that this gene is a lncRNA tumor suppressor. [provided by RefSeq, Mar 2012]

MEG3 links:

ENSG00000258663 (HGNC:):

ENSG00000258663 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 14-100835270-GC-G is Benign according to our data. Variant chr14-100835270-GC-G is described in ClinVar as [Likely_benign]. Clinvar id is 2644541.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
MEG3	NR_002766.2 link	n.1050-890delC	intron_variant	Intron 4 of 6
MEG3	NR_003530.2 link	n.1299+526delC	intron_variant	Intron 6 of 8
MEG3	NR_003531.3 link	n.1026-462delC	intron_variant	Intron 4 of 7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
MEG3	ENST00000398461.5 link	n.2309delC	non_coding_transcript_exon_variant	Exon 1 of 4	1
MEG3	ENST00000429159.6 link	n.1066-890delC	intron_variant	Intron 4 of 6	1
MEG3	ENST00000451743.6 link	n.1032-890delC	intron_variant	Intron 4 of 6	1

Frequencies

GnomAD3 genomes

AF:

0.00755

AC:

1148

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00713

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0337

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00907

Gnomad OTH

AF:

0.00478

GnomAD4 exome

AF:

0.00371

AC:

AN:

6736

Hom.:

Cov.:

AF XY:

0.00304

AC XY:

AN XY:

3622

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00877

Gnomad4 NFE exome

AF:

0.00466

Gnomad4 OTH exome

AF:

0.00518

GnomAD4 genome

AF:

0.00755

AC:

1149

AN:

152196

Hom.:

Cov.:

AF XY:

0.00906

AC XY:

674

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00713

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0337

Gnomad4 NFE

AF:

0.00907

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00517

Hom.:

Bravo

AF:

0.00518

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MEG3: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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