rs267607234

Variant names:

• chr11-64805745-CC-TT
• rs267607234
• NM_001370259.2:c.1074_1075delGGinsAA

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1 PP2 PP5

The NM_001370259.2(MEN1):​c.1074_1075delGGinsAA​(p.Glu359Lys) 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. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. E358E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MEN1 NM_001370259.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.19
• Publications: 4 publications found

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]

MEN1 Gene-Disease associations (from GenCC):

• multiple endocrine neoplasia type 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet, Ambry Genetics
• familial isolated hyperparathyroidism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• pituitary gigantism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary pheochromocytoma-paraganglioma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM1: In a hotspot region, there are 6 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 2 benign, 19 uncertain in NM_001370259.2
• PP2: Missense variant in the MEN1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 113 curated pathogenic missense variants (we use a threshold of 10). The gene has 20 curated benign missense variants. Trascript score misZ: 4.1921 (above the threshold of 3.09). GenCC associations: The gene is linked to multiple endocrine neoplasia type 1, hereditary pheochromocytoma-paraganglioma, pituitary gigantism, familial isolated hyperparathyroidism.
• PP5: Variant 11-64805745-CC-TT is Pathogenic according to our data. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-64805745-CC-TT is described in CliVar as Pathogenic. Clinvar id is 16695.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEN1	NM_001370259.2	c.1074_1075delGGinsAA	p.Glu359Lys	missense_variant		ENST00000450708.7	NP_001357188.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEN1	ENST00000450708.7	c.1074_1075delGGinsAA	p.Glu359Lys	missense_variant		5	NM_001370259.2	ENSP00000394933.3

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

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Angiofibroma, somatic Pathogenic:1

Sep 01, 1998

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.2
Mutation Taster		=0/100	disease causing

Splicing

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

Other links and lift over

dbSNP: rs267607234; hg19: chr11-64573217; COSMIC: COSV53648733;