19-2432452-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032737.4(LMNB2):c.1554G>C(p.Thr518Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00544 in 1,613,582 control chromosomes in the GnomAD database, including 441 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T518T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.029 ( 235 hom., cov: 31)

Exomes 𝑓: 0.0030 ( 206 hom. )

Consequence

LMNB2
NM_032737.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.992

Publications

1 publications found

Variant links:

Genes affected

LMNB2 (HGNC:6638): (lamin B2) This gene encodes a B type nuclear lamin. The nuclear lamina consists of a two-dimensional matrix of proteins located next to the inner nuclear membrane. The lamin family of proteins make up the matrix and are highly conserved in evolution. During mitosis, the lamina matrix is reversibly disassembled as the lamin proteins are phosphorylated. Lamin proteins are thought to be involved in nuclear stability, chromatin structure and gene expression. Vertebrate lamins consist of two types, A and B. Mutations in this gene are associated with acquired partial lipodystrophy. [provided by RefSeq, May 2012]

LMNB2 Gene-Disease associations (from GenCC):

microcephaly 27, primary, autosomal dominant
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
progressive myoclonic epilepsy type 9
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
microcephaly
Inheritance: AD Classification: MODERATE Submitted by: Franklin by Genoox
lipodystrophy, partial, acquired, susceptibility to
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
central nervous system malformation
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

LMNB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 19-2432452-C-G is Benign according to our data. Variant chr19-2432452-C-G is described in ClinVar as [Benign]. Clinvar id is 475776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.992 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMNB2	NM_032737.4 link	c.1554G>C	p.Thr518Thr	synonymous_variant	Exon 9 of 12	ENST00000325327.4	NP_116126.3	Q03252

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LMNB2	ENST00000325327.4 link	c.1554G>C	p.Thr518Thr	synonymous_variant	Exon 9 of 12	1	NM_032737.4	ENSP00000327054.3	Q03252
LMNB2	ENST00000532465.1 link	n.146G>C		non_coding_transcript_exon_variant	Exon 2 of 5	3
LMNB2	ENST00000490554.5 link	n.*56G>C		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0289

AC:

4395

AN:

151844

Hom.:

232

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.0234

GnomAD2 exomes

AF:

0.00776

AC:

1949

AN:

251148

AF XY:

0.00564

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.00547

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000158

Gnomad OTH exome

AF:

0.00293

GnomAD4 exome

AF:

0.00298

AC:

4350

AN:

1461620

Hom.:

206

Cov.:

AF XY:

0.00261

AC XY:

1899

AN XY:

727134

show subpopulations

African (AFR)

AF:

0.106

AC:

3542

AN:

33474

American (AMR)

AF:

0.00590

AC:

264

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000232

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53232

Middle Eastern (MID)

AF:

0.00295

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000845

AC:

AN:

1111958

Other (OTH)

AF:

0.00682

AC:

412

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

244

488

733

977

1221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

228

342

456

570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0291

AC:

4423

AN:

151962

Hom.:

235

Cov.:

AF XY:

0.0281

AC XY:

2084

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.101

AC:

4190

AN:

41376

American (AMR)

AF:

0.0109

AC:

166

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.000415

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000221

AC:

AN:

67964

Other (OTH)

AF:

0.0232

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

203

406

609

812

1015

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00177

Hom.:

Bravo

AF:

0.0333

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Lipodystrophy, partial, acquired, susceptibility to;C4225289:Progressive myoclonic epilepsy type 9

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Oct 04, 2024

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.12

(source)

DANN

Benign

0.73

PhyloP100

-0.99

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over