chr5-36108599-G-C

Position:

• chr5-36108599-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001007527.2(LMBRD2):​c.1832C>G​(p.Thr611Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LMBRD2 NM_001007527.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.98

Genes affected

LMBRD2 (HGNC:25287): (LMBR1 domain containing 2) Involved in adrenergic receptor signaling pathway. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.102832526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMBRD2	NM_001007527.2	c.1832C>G	p.Thr611Ser	missense_variant	16/18	ENST00000296603.5	NP_001007528.1
LMBRD2	XM_011514162.3	c.1832C>G	p.Thr611Ser	missense_variant	16/18		XP_011512464.1
LMBRD2	XM_047417877.1	c.1169C>G	p.Thr390Ser	missense_variant	12/14		XP_047273833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMBRD2	ENST00000296603.5	c.1832C>G	p.Thr611Ser	missense_variant	16/18	1	NM_001007527.2	ENSP00000296603.4
LMBRD2	ENST00000505524.1	n.293C>G		non_coding_transcript_exon_variant	5/5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental delay with variable neurologic and brain abnormalities Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Neuberg Centre For Genomic Medicine, NCGM

Jul 22, 2023

The missense variant c.1832C>G p.Thr611Ser in LMBRD2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The observed variant is absent in gnomAD exomes database. This variant has not been submitted to the ClinVar database. Multiple lines of computational evidence Polyphen - benign, SIFT - tolerated and MutationTaster - polymophism predicts no evidence on protein structure and function for this variant. The amino acid change p.Thr611Ser in LMBRD2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Thr at position 611 is changed to a Ser changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Uncertain Significance VUS. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.0089	T
Eigen	Benign	-0.19
Eigen_PC	Benign	0.079
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.087
Sift	Benign	0.51	T
Sift4G	Benign	0.99	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.21		Loss of glycosylation at S610 (P = 0.0582);
MVP		0.32
MPC		0.28
ClinPred		0.73	D
GERP RS		5.7
Varity_R		0.11
gMVP		0.20

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-36108701;