chr1-240092271-C-G

Variant names:

• chr1-240092271-C-G
• rs1465821580
• NM_020066.5:c.162C>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_020066.5(FMN2):​c.162C>G​(p.Gly54Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000094 (0 hom.)
• Consequence: FMN2 NM_020066.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.709
• Publications: 2 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 1-240092271-C-G is Benign according to our data. Variant chr1-240092271-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2578603.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.709 with no splicing effect.

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.162C>G	p.Gly54Gly	synonymous	Exon 1 of 18	NP_064450.3
	FMN2	NM_001305424.2		c.162C>G	p.Gly54Gly	synonymous	Exon 1 of 19	NP_001292353.1
	FMN2	NM_001348094.2		c.162C>G	p.Gly54Gly	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.162C>G	p.Gly54Gly	synonymous	Exon 1 of 18	ENSP00000318884.9	Q9NZ56-1
	FMN2	ENST00000447095.5	TSL:3	c.-87+24198C>G		intron	N/A	ENSP00000409308.1	B0QZA8

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000939 AC: 1 AN: 106530 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 52184

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 1980

American (AMR) AF: 0.00 AC: 0 AN: 1630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1580

East Asian (EAS) AF: 0.00 AC: 0 AN: 10694

South Asian (SAS) AF: 0.00 AC: 0 AN: 5690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1250

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 376

European-Non Finnish (NFE) AF: 0.0000127 AC: 1 AN: 78816

Other (OTH) AF: 0.00 AC: 0 AN: 4514

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

Alfa AF: 0.0879 Hom.: 0

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	-0.60
CADD	Benign	11
DANN	Benign	0.78
PhyloP100		-0.71
PromoterAI		-0.065	Neutral
Mutation Taster		=100/0	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: rs1465821580; hg19: chr1-240255571;