19-2430639-C-T

Variant names:

• chr19-2430639-C-T
• rs1049910
• NM_032737.4:c.*272G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032737.4(LMNB2):​c.*272G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000499 in 541,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: LMNB2 NM_032737.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.29
• Publications: 12 publications found

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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• progressive myoclonic epilepsy type 9

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• microcephaly

  Inheritance: AD Classification: MODERATE Submitted by: Franklin by Genoox
• lipodystrophy, partial, acquired, susceptibility to

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• central nervous system malformation

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032737.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMNB2	NM_032737.4	MANE Select	c.*272G>A		3_prime_UTR	Exon 12 of 12	NP_116126.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMNB2	ENST00000325327.4	TSL:1 MANE Select	c.*272G>A		3_prime_UTR	Exon 12 of 12	ENSP00000327054.3	Q03252
	LMNB2	ENST00000917224.1		c.*272G>A		3_prime_UTR	Exon 13 of 13	ENSP00000587283.1
	LMNB2	ENST00000917223.1		c.*272G>A		3_prime_UTR	Exon 12 of 12	ENSP00000587282.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152072 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000565 AC: 22 AN: 389224 Hom.: 0 Cov.: 0 AF XY: 0.0000434 AC XY: 9 AN XY: 207234

African (AFR) AF: 0.0000894 AC: 1 AN: 11190

American (AMR) AF: 0.000951 AC: 19 AN: 19978

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12372

East Asian (EAS) AF: 0.00 AC: 0 AN: 24788

South Asian (SAS) AF: 0.0000437 AC: 2 AN: 45764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 229662

Other (OTH) AF: 0.00 AC: 0 AN: 22172

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152072 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74258

African (AFR) AF: 0.0000483 AC: 2 AN: 41414

American (AMR) AF: 0.000197 AC: 3 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 710

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.16
DANN	Benign	0.94
PhyloP100		-3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs1049910; hg19: chr19-2430637;