19-2430639-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032737.4(LMNB2):​c.*272G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 540,632 control chromosomes in the GnomAD database, including 60,296 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17344 hom., cov: 33)
  • Exomes 𝑓: 0.46 (42952 hom.)
• Consequence: LMNB2 NM_032737.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 19-2430639-C-G is Benign according to our data. Variant chr19-2430639-C-G is described in ClinVar as Benign. ClinVar VariationId is 1245133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

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

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71369 AN: 152008 Hom.: 17325 Cov.: 33

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.425

GnomAD4 exome AF: 0.460 AC: 178592 AN: 388506 Hom.: 42952 Cov.: 0 AF XY: 0.470 AC XY: 97125 AN XY: 206862

African (AFR) AF: 0.558 AC: 6236 AN: 11168

American (AMR) AF: 0.332 AC: 6623 AN: 19942

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 4063 AN: 12344

East Asian (EAS) AF: 0.673 AC: 16635 AN: 24732

South Asian (SAS) AF: 0.603 AC: 27602 AN: 45738

European-Finnish (FIN) AF: 0.421 AC: 9075 AN: 21558

Middle Eastern (MID) AF: 0.440 AC: 744 AN: 1692

European-Non Finnish (NFE) AF: 0.427 AC: 97812 AN: 229220

Other (OTH) AF: 0.443 AC: 9802 AN: 22112

GnomAD4 genome AF: 0.470 AC: 71440 AN: 152126 Hom.: 17344 Cov.: 33 AF XY: 0.474 AC XY: 35236 AN XY: 74356

African (AFR) AF: 0.563 AC: 23381 AN: 41512

American (AMR) AF: 0.371 AC: 5670 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1107 AN: 3472

East Asian (EAS) AF: 0.646 AC: 3347 AN: 5178

South Asian (SAS) AF: 0.620 AC: 2990 AN: 4826

European-Finnish (FIN) AF: 0.423 AC: 4478 AN: 10576

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.427 AC: 29022 AN: 67984

Other (OTH) AF: 0.424 AC: 893 AN: 2108

Alfa AF: 0.299 Hom.: 710

Bravo AF: 0.462

Asia WGS AF: 0.589 AC: 2046 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.066
DANN	Benign	0.65
PhyloP100		-3.3
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

Other links and lift over

dbSNP: rs1049910; hg19: chr19-2430637; COSMIC: COSV53115542; COSMIC: COSV53115542;