19-2432452-C-G

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

2

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

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
LMNB2NM_032737.4 linkc.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 Appris UniProt
LMNB2ENST00000325327.4 linkc.1554G>C p.Thr518Thr synonymous_variant Exon 9 of 12 1 NM_032737.4 ENSP00000327054.3 Q03252
LMNB2ENST00000532465.1 linkn.146G>C non_coding_transcript_exon_variant Exon 2 of 5 3
LMNB2ENST00000490554.5 linkn.*56G>C downstream_gene_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0289
AC:
4395
AN:
151844
Hom.:
232
Cov.:
31
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.:
33
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:
0
AN:
26130
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39700
South Asian (SAS)
AF:
0.000232
AC:
20
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53232
Middle Eastern (MID)
AF:
0.00295
AC:
17
AN:
5764
European-Non Finnish (NFE)
AF:
0.0000845
AC:
94
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
0
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
0
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.:
31
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:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5160
South Asian (SAS)
AF:
0.000415
AC:
2
AN:
4814
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10596
Middle Eastern (MID)
AF:
0.00340
AC:
1
AN:
294
European-Non Finnish (NFE)
AF:
0.000221
AC:
15
AN:
67964
Other (OTH)
AF:
0.0232
AC:
49
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
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
0
46
92
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.:
3
Bravo
AF:
0.0333
Asia WGS
AF:
0.00606
AC:
21
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
DANN
Benign
0.73
PhyloP100
-0.99
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs11882908; hg19: chr19-2432450; API