19-2430639-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032737.4(LMNB2):​c.*272G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LMNB2 NM_032737.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.29
• Publications: 0 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

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>T		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>T		3_prime_UTR	Exon 12 of 12	ENSP00000327054.3	Q03252
	LMNB2	ENST00000917224.1		c.*272G>T		3_prime_UTR	Exon 13 of 13	ENSP00000587283.1
	LMNB2	ENST00000917223.1		c.*272G>T		3_prime_UTR	Exon 12 of 12	ENSP00000587282.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 389224 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 207234

African (AFR) AF: 0.00 AC: 0 AN: 11190

American (AMR) AF: 0.00 AC: 0 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: 0.00 AC: 0 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 Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.060
DANN	Benign	0.38
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;