5-36143290-CAG-TAA

Variant names:

• chr5-36143290-CAG-TAA
• NM_001007527.2:c.58_60delCTGinsTTA
• LMBRD2 p.21

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001007527.2(LMBRD2):​c.58_60delCTGinsTTA​(p.21) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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: 32)
• Consequence: LMBRD2 NM_001007527.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.59
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.58_60delCTGinsTTA	p.21	synonymous	N/A	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.58_60delCTGinsTTA	p.21	synonymous	N/A	ENSP00000296603.4	Q68DH5
	LMBRD2	ENST00000885486.1		c.58_60delCTGinsTTA	p.21	synonymous	N/A	ENSP00000555545.1
	LMBRD2	ENST00000885487.1		c.58_60delCTGinsTTA	p.21	synonymous	N/A	ENSP00000555546.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.6

Splicing

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: chr5-36143392;