1-240092268-GGGCGGC-GGGCGGCGGC

Variant names:

• chr1-240092268-G-GGGC
• rs71929261
• NM_020066.5:c.174_176dupCGG

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_020066.5(FMN2):​c.174_176dupCGG​(p.Gly59dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G59G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: FMN2 NM_020066.5 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03
• Publications: 0 publications found

Genes affected

FMN2 (HGNC:14074): (formin 2) This gene is a member of the formin homology protein family. The encoded protein is thought to have essential roles in organization of the actin cytoskeleton and in cell polarity. This protein mediates the formation of an actin mesh that positions the spindle during oogenesis and also regulates the formation of actin filaments in the nucleus. This protein also forms a perinuclear actin/focal-adhesion system that regulates the shape and position of the nucleus during cell migration. Mutations in this gene have been associated with infertility and also with an autosomal recessive form of intellectual disability (MRT47). Alternatively spliced transcript variants have been identified. [provided by RefSeq, Jul 2017]

FMN2 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 47

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_020066.5

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020066.5. 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
	FMN2	NM_020066.5	MANE Select	c.174_176dupCGG	p.Gly59dup	disruptive_inframe_insertion	Exon 1 of 18	NP_064450.3
	FMN2	NM_001305424.2		c.174_176dupCGG	p.Gly59dup	disruptive_inframe_insertion	Exon 1 of 19	NP_001292353.1
	FMN2	NM_001348094.2		c.174_176dupCGG	p.Gly59dup	disruptive_inframe_insertion	Exon 1 of 15	NP_001335023.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMN2	ENST00000319653.14	TSL:5 MANE Select	c.174_176dupCGG	p.Gly59dup	disruptive_inframe_insertion	Exon 1 of 18	ENSP00000318884.9	Q9NZ56-1
	FMN2	ENST00000447095.5	TSL:3	c.-87+24210_-87+24212dupCGG		intron	N/A	ENSP00000409308.1	B0QZA8

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000282 AC: 4 AN: 1416164 Hom.: 0 Cov.: 0 AF XY: 0.00000428 AC XY: 3 AN XY: 700204

African (AFR) AF: 0.0000306 AC: 1 AN: 32708

American (AMR) AF: 0.00 AC: 0 AN: 39010

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24874

East Asian (EAS) AF: 0.00 AC: 0 AN: 38428

South Asian (SAS) AF: 0.00 AC: 0 AN: 80530

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5052

European-Non Finnish (NFE) AF: 0.00000184 AC: 2 AN: 1089068

Other (OTH) AF: 0.0000171 AC: 1 AN: 58538

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0

Splicing

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

Other links and lift over

dbSNP: rs71929261; hg19: chr1-240255568;