chr1-240092193-G-A

Variant names:

• chr1-240092193-G-A
• rs757156181
• NM_020066.5:c.84G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_020066.5(FMN2):​c.84G>A​(p.Gly28Gly) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000316 in 1,582,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FMN2 NM_020066.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.02
• 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), G2P, Ambry Genetics
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 1-240092193-G-A is Benign according to our data. Variant chr1-240092193-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 729042.Status of the report is criteria_provided_single_submitter, 1 stars.

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.84G>A	p.Gly28Gly	synonymous	Exon 1 of 18	NP_064450.3
	FMN2	NM_001305424.2		c.84G>A	p.Gly28Gly	synonymous	Exon 1 of 19	NP_001292353.1
	FMN2	NM_001348094.2		c.84G>A	p.Gly28Gly	synonymous	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.84G>A	p.Gly28Gly	synonymous	Exon 1 of 18	ENSP00000318884.9	Q9NZ56-1
	FMN2	ENST00000447095.5	TSL:3	c.-87+24120G>A		intron	N/A	ENSP00000409308.1	B0QZA8

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151608 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000104 AC: 2 AN: 193084 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000680

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000210 AC: 3 AN: 1431184 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 708630

African (AFR) AF: 0.00 AC: 0 AN: 33134

American (AMR) AF: 0.0000742 AC: 3 AN: 40416

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25282

East Asian (EAS) AF: 0.00 AC: 0 AN: 38818

South Asian (SAS) AF: 0.00 AC: 0 AN: 81826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49470

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5324

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097696

Other (OTH) AF: 0.00 AC: 0 AN: 59218

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151608 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74048

African (AFR) AF: 0.00 AC: 0 AN: 41220

American (AMR) AF: 0.000131 AC: 2 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5094

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67906

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	13
DANN	Benign	0.91
PhyloP100		6.0
PromoterAI		-0.044	Neutral
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs757156181; hg19: chr1-240255493;