rs542821471

Variant names:

• chr19-2430956-CAGGAAGGA-C
• rs542821471
• NM_032737.4:c.1822-12_1822-5delTCCTTCCT

Your query was ambiguous. Multiple possible variants found:

• chr19-2430956-CAGGAAGGA-C
• chr19-2430956-CAGGAAGGA-CAGGA
• chr19-2430956-CAGGAAGGA-CAGGAAGGAAGGA
• chr19-2430956-CAGGAAGGA-CAGGAAGGAAGGAAGGA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032737.4(LMNB2):​c.1822-12_1822-5delTCCTTCCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,084 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LMNB2 NM_032737.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1822-12_1822-5delTCCTTCCT		splice_region intron	N/A	NP_116126.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMNB2	ENST00000325327.4	TSL:1 MANE Select	c.1822-12_1822-5delTCCTTCCT		splice_region intron	N/A	ENSP00000327054.3	Q03252
	LMNB2	ENST00000917224.1		c.1963-12_1963-5delTCCTTCCT		splice_region intron	N/A	ENSP00000587283.1
	LMNB2	ENST00000917223.1		c.1828-12_1828-5delTCCTTCCT		splice_region intron	N/A	ENSP00000587282.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248840 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455084 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 724230

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33326

American (AMR) AF: 0.0000224 AC: 1 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5398

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106324

Other (OTH) AF: 0.00 AC: 0 AN: 60128

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs542821471; hg19: chr19-2430954;