NM_138621.5:c.82_84delCTCinsGTG

Variant names:

• chr2-111123827-CTC-GTG
• NM_138621.5:c.82_84delCTCinsGTG
• BCL2L11 p.Leu28Val

Variant summary

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

The NM_138621.5(BCL2L11):​c.82_84delCTCinsGTG​(p.Leu28Val) variant causes a missense change. 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BCL2L11 NM_138621.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.59
• Publications: 0 publications found

Genes affected

BCL2L11 (HGNC:994): (BCL2 like 11) The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The protein encoded by this gene contains a Bcl-2 homology domain 3 (BH3). It has been shown to interact with other members of the BCL-2 protein family and to act as an apoptotic activator. The expression of this gene can be induced by nerve growth factor (NGF), as well as by the forkhead transcription factor FKHR-L1, which suggests a role of this gene in neuronal and lymphocyte apoptosis. Transgenic studies of the mouse counterpart suggested that this gene functions as an essential initiator of apoptosis in thymocyte-negative selection. Several alternatively spliced transcript variants of this gene have been identified. [provided by RefSeq, Jun 2013]

MIR4435-2HG (HGNC:35163): (MIR4435-2 host gene)

ENSG00000293584 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138621.5. 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
	BCL2L11	NM_138621.5	MANE Select	c.82_84delCTCinsGTG	p.Leu28Val	missense	N/A	NP_619527.1	O43521-1
	BCL2L11	NM_001204108.1		c.82_84delCTCinsGTG	p.Leu28Val	missense	N/A	NP_001191037.1	O43521-8
	BCL2L11	NM_138622.4		c.82_84delCTCinsGTG	p.Leu28Val	missense	N/A	NP_619528.1	O43521-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2L11	ENST00000393256.8	TSL:1 MANE Select	c.82_84delCTCinsGTG	p.Leu28Val	missense	N/A	ENSP00000376943.2	O43521-1
	BCL2L11	ENST00000405953.6	TSL:1	c.82_84delCTCinsGTG	p.Leu28Val	missense	N/A	ENSP00000384641.1	O43521-17
	BCL2L11	ENST00000361493.10	TSL:1	n.82_84delCTCinsGTG		non_coding_transcript_exon	Exon 1 of 4	ENSP00000354879.6	A0A0C4DH20

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.6

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: chr2-111881404;