19-2430956-C-CAGGA

Position:

• chr19-2430956-C-CAGGA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_032737.4(LMNB2):​c.1822-5_1822-4insTCCT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000213 in 1,607,312 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: LMNB2 NM_032737.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.320

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 19-2430956-C-CAGGA is Benign according to our data. Variant chr19-2430956-C-CAGGA is described in ClinVar as [Likely_benign]. Clinvar id is 740622.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMNB2	NM_032737.4	c.1822-5_1822-4insTCCT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000325327.4	NP_116126.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMNB2	ENST00000325327.4	c.1822-5_1822-4insTCCT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_032737.4	ENSP00000327054	P1
LMNB2	ENST00000475819.1	n.48-649_48-648insTCCT		intron_variant, non_coding_transcript_variant		5
LMNB2	ENST00000532465.1	n.413+591_413+592insTCCT		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.000256 AC: 39 AN: 152148 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000225 AC: 56 AN: 248840 Hom.: 0 AF XY: 0.000230 AC XY: 31 AN XY: 134844

Gnomad AFR exome AF: 0.000186

Gnomad AMR exome AF: 0.0000871

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000278

Gnomad NFE exome AF: 0.000394

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000209 AC: 304 AN: 1455046 Hom.: 0 Cov.: 28 AF XY: 0.000228 AC XY: 165 AN XY: 724212

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.0000671

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.000150

Gnomad4 NFE exome AF: 0.000255

Gnomad4 OTH exome AF: 0.000116

GnomAD4 genome AF: 0.000256 AC: 39 AN: 152266 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9 AN XY: 74442

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.00

EpiCase AF: 0.000709

EpiControl AF: 0.000416

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Lipodystrophy, partial, acquired, susceptibility to;C4225289:Progressive myoclonic epilepsy type 9 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs542821471; hg19: chr19-2430954;