5-36143292-G-A

Variant names:

• chr5-36143292-G-A
• NM_001007527.2:c.58C>T
• LMBRD2 p.Leu20Leu

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001007527.2(LMBRD2):​c.58C>T​(p.Leu20Leu) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L20L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LMBRD2 NM_001007527.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.93
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• developmental delay with variable neurologic and brain abnormalities

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• neurodevelopmental disorder with microcephaly and dysmorphic facies

  Inheritance: AD Classification: MODERATE Submitted by: Franklin by Genoox
• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: Illumina

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP7: Synonymous conserved (PhyloP=2.93 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007527.2. 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
	LMBRD2	NM_001007527.2	MANE Select	c.58C>T	p.Leu20Leu	synonymous	Exon 2 of 18	NP_001007528.1	Q68DH5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMBRD2	ENST00000296603.5	TSL:1 MANE Select	c.58C>T	p.Leu20Leu	synonymous	Exon 2 of 18	ENSP00000296603.4	Q68DH5
	LMBRD2	ENST00000885486.1		c.58C>T	p.Leu20Leu	synonymous	Exon 2 of 18	ENSP00000555545.1
	LMBRD2	ENST00000885487.1		c.58C>T	p.Leu20Leu	synonymous	Exon 2 of 18	ENSP00000555546.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	9.3
DANN	Benign	0.76
PhyloP100		2.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-36143394;

COSMIC: COSV104616116;

COSMIC: COSV104616116;