5-36108600-T-C

Position:

• chr5-36108600-T-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.1831A>G​(p.Thr611Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 2.59

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]

LMBRD2 (HGNC:):

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=0.09531972).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMBRD2	NM_001007527.2	c.1831A>G	p.Thr611Ala	missense_variant	16/18	ENST00000296603.5	NP_001007528.1
LMBRD2	XM_011514162.3	c.1831A>G	p.Thr611Ala	missense_variant	16/18		XP_011512464.1
LMBRD2	XM_047417877.1	c.1168A>G	p.Thr390Ala	missense_variant	12/14		XP_047273833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMBRD2	ENST00000296603.5	c.1831A>G	p.Thr611Ala	missense_variant	16/18	1	NM_001007527.2	ENSP00000296603.4
LMBRD2	ENST00000505524.1	n.292A>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

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Feb 10, 2023

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.017
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.41	N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.048
Sift	Benign	0.19	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.22		Loss of phosphorylation at T611 (P = 0.0083);
MVP		0.26
MPC		0.31
ClinPred		0.66	D
GERP RS		5.7
Varity_R		0.056
gMVP		0.26

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: chr5-36108702;