11-64809987-CAGCACCAAGGAAAGG-CAGCACCAAGGAAAGGAGCACCAAGGAAAGG

Variant names:

• chr11-64809987-C-CAGCACCAAGGAAAGG
• rs1555166695
• NM_001370259.2:c.108_122dupCCTTTCCTTGGTGCT

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_001370259.2(MEN1):​c.108_122dupCCTTTCCTTGGTGCT​(p.Leu41_Gly42insLeuSerLeuValLeu) variant causes a disruptive inframe insertion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: MEN1 NM_001370259.2 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 5.59

Genes affected

MEN1 (HGNC:7010): (menin 1) This gene encodes menin, a tumor suppressor associated with a syndrome known as multiple endocrine neoplasia type 1. Menin is a scaffold protein that functions in histone modification and epigenetic gene regulation. It is thought to regulate several pathways and processes by altering chromatin structure through the modification of histones. [provided by RefSeq, May 2019]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001370259.2.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEN1	NM_001370259.2	c.108_122dupCCTTTCCTTGGTGCT	p.Leu41_Gly42insLeuSerLeuValLeu	disruptive_inframe_insertion	Exon 2 of 10	ENST00000450708.7	NP_001357188.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEN1	ENST00000450708.7	c.108_122dupCCTTTCCTTGGTGCT	p.Leu41_Gly42insLeuSerLeuValLeu	disruptive_inframe_insertion	Exon 2 of 10	5	NM_001370259.2	ENSP00000394933.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Uncertain:1

Dec 19, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: MEN1 c.108_122dup15 (p.Leu37_Leu41dup; also described as 34-38ins: 5aa in the literature) results in an in-frame duplication that is predicted to duplicate 5 amino acids into the encoded protein. The variant was absent in 220222 control chromosomes (gnomAD). c.108_122dup15 has been reported in the literature in individuals affected with multiple endocrine neoplasia Type 1 (examples: Bassett _1998, Internal data). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 9463336, 12112656, 10730900). ClinVar contains an entry for this variant (Variation ID: 527284). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. -

Multiple endocrine neoplasia, type 1 Uncertain:1

Aug 11, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is also known as "34-38: ins5aa". In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 527284). This variant has been observed in individual(s) with multiple endocrine neoplasia type 1 (PMID: 9463336). This variant is not present in population databases (gnomAD no frequency). This variant, c.108_122dup, results in the insertion of 5 amino acid(s) of the MEN1 protein (p.Leu37_Leu41dup), but otherwise preserves the integrity of the reading frame. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1555166695; hg19: chr11-64577459;