22-27799614-A-ATGCTGC

Variant names:

• chr22-27799614-A-ATGCTGC
• rs747503495
• NM_002430.3:c.924_929dupGCAGCA

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3 BS2

The NM_002430.3(MN1):​c.924_929dupGCAGCA​(p.Gln308_Gln309dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.00000719 in 1,390,046 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: MN1 NM_002430.3 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.02
• Publications: 2 publications found

Genes affected

MN1 (HGNC:7180): (MN1 proto-oncogene, transcriptional regulator) Meningioma 1 (MN1) contains two sets of CAG repeats. It is disrupted by a balanced translocation (4;22) in a meningioma, and its inactivation may contribute to meningioma 32 pathogenesis. [provided by RefSeq, Jul 2008]

MN1 Gene-Disease associations (from GenCC):

• CEBALID syndrome

  Inheritance: AD Classification: STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• familial meningioma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_002430.3
• BS2: High AC in GnomAdExome4 at 10 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002430.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MN1	NM_002430.3	MANE Select	c.924_929dupGCAGCA	p.Gln308_Gln309dup	disruptive_inframe_insertion	Exon 1 of 2	NP_002421.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MN1	ENST00000302326.5	TSL:1 MANE Select	c.924_929dupGCAGCA	p.Gln308_Gln309dup	disruptive_inframe_insertion	Exon 1 of 2	ENSP00000304956.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000891 AC: 1 AN: 112286 AF XY: 0.0000168

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000245

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000719 AC: 10 AN: 1390046 Hom.: 0 Cov.: 33 AF XY: 0.00000584 AC XY: 4 AN XY: 685010

African (AFR) AF: 0.0000318 AC: 1 AN: 31410

American (AMR) AF: 0.00 AC: 0 AN: 35088

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24638

East Asian (EAS) AF: 0.00 AC: 0 AN: 35600

South Asian (SAS) AF: 0.00 AC: 0 AN: 77836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5572

European-Non Finnish (NFE) AF: 0.00000465 AC: 5 AN: 1074312

Other (OTH) AF: 0.0000694 AC: 4 AN: 57632

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.0

Splicing

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

Other links and lift over

dbSNP: rs747503495; hg19: chr22-28195602;