5-36137518-A-T

Variant names:

• chr5-36137518-A-T
• rs267759
• NM_001007527.2:c.369-77T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001007527.2(LMBRD2):​c.369-77T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000133 in 750,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000013 (0 hom.)
• Consequence: LMBRD2 NM_001007527.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.499
• 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, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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.369-77T>A		intron	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.369-77T>A		intron	N/A	ENSP00000296603.4	Q68DH5
	LMBRD2	ENST00000885486.1		c.369-77T>A		intron	N/A	ENSP00000555545.1
	LMBRD2	ENST00000885487.1		c.369-77T>A		intron	N/A	ENSP00000555546.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000133 AC: 1 AN: 750590 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 378712

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 18890

American (AMR) AF: 0.00 AC: 0 AN: 23358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14802

East Asian (EAS) AF: 0.00 AC: 0 AN: 34216

South Asian (SAS) AF: 0.00 AC: 0 AN: 31734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2516

European-Non Finnish (NFE) AF: 0.00000182 AC: 1 AN: 550792

Other (OTH) AF: 0.00 AC: 0 AN: 33318

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.72
DANN	Benign	0.35
PhyloP100		0.50

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

Other links and lift over

dbSNP: rs267759; hg19: chr5-36137620;