19-2431172-G-A

Variant names:

• chr19-2431172-G-A
• rs60073269
• NM_032737.4:c.1822-220C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032737.4(LMNB2):​c.1822-220C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0595 in 152,272 control chromosomes in the GnomAD database, including 425 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.060 (425 hom., cov: 33)
• Consequence: LMNB2 NM_032737.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.669
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 19-2431172-G-A is Benign according to our data. Variant chr19-2431172-G-A is described in ClinVar as Benign. ClinVar VariationId is 1229867.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.248 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.1822-220C>T		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.1822-220C>T		intron	N/A	ENSP00000327054.3	Q03252
	LMNB2	ENST00000917224.1		c.1963-220C>T		intron	N/A	ENSP00000587283.1
	LMNB2	ENST00000917223.1		c.1828-220C>T		intron	N/A	ENSP00000587282.1

Frequencies

GnomAD3 genomes AF: 0.0595 AC: 9058 AN: 152154 Hom.: 426 Cov.: 33

Gnomad AFR AF: 0.0676

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0636

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0367

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0408

Gnomad OTH AF: 0.0406

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0595 AC: 9062 AN: 152272 Hom.: 425 Cov.: 33 AF XY: 0.0622 AC XY: 4633 AN XY: 74460

African (AFR) AF: 0.0675 AC: 2805 AN: 41536

American (AMR) AF: 0.0634 AC: 970 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0349 AC: 121 AN: 3470

East Asian (EAS) AF: 0.260 AC: 1346 AN: 5182

South Asian (SAS) AF: 0.110 AC: 533 AN: 4830

European-Finnish (FIN) AF: 0.0367 AC: 390 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0408 AC: 2772 AN: 68016

Other (OTH) AF: 0.0440 AC: 93 AN: 2116

Alfa AF: 0.0197 Hom.: 7

Bravo AF: 0.0600

Asia WGS AF: 0.167 AC: 581 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.7
DANN	Benign	0.68
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs60073269; hg19: chr19-2431170;