rs188083977

Variant names:

• chr1-240207635-A-C
• rs188083977
• NM_020066.5:c.2823A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-240207635-A-C
• chr1-240207635-A-G
• chr1-240207635-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_020066.5(FMN2):​c.2823A>C​(p.Gly941Gly) 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: 𝑓 0.0072 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00099 (12 hom.)
  • Failed GnomAD Quality Control
• Consequence: FMN2 NM_020066.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.845
• Publications: 5 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-240207635-A-C is Benign according to our data. Variant chr1-240207635-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 435227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.845 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMN2	NM_020066.5	c.2823A>C	p.Gly941Gly	synonymous_variant	Exon 5 of 18	ENST00000319653.14	NP_064450.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMN2	ENST00000319653.14	c.2823A>C	p.Gly941Gly	synonymous_variant	Exon 5 of 18	5	NM_020066.5	ENSP00000318884.9

Frequencies

GnomAD3 genomes AF: 0.00728 AC: 312 AN: 42832 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00942

Gnomad AMI AF: 0.0108

Gnomad AMR AF: 0.00633

Gnomad ASJ AF: 0.00643

Gnomad EAS AF: 0.00923

Gnomad SAS AF: 0.00835

Gnomad FIN AF: 0.00998

Gnomad MID AF: 0.0400

Gnomad NFE AF: 0.00610

Gnomad OTH AF: 0.00530

GnomAD2 exomes AF: 0.000548 AC: 116 AN: 211838 AF XY: 0.000504

Gnomad AFR exome AF: 0.000227

Gnomad AMR exome AF: 0.000413

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000339

Gnomad FIN exome AF: 0.000207

Gnomad NFE exome AF: 0.000757

Gnomad OTH exome AF: 0.00142

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000989 AC: 856 AN: 865086 Hom.: 12 Cov.: 36 AF XY: 0.000961 AC XY: 407 AN XY: 423356

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

African (AFR) AF: 0.00102 AC: 15 AN: 14740

American (AMR) AF: 0.00137 AC: 37 AN: 27094

Ashkenazi Jewish (ASJ) AF: 0.00170 AC: 15 AN: 8822

East Asian (EAS) AF: 0.00180 AC: 22 AN: 12226

South Asian (SAS) AF: 0.00213 AC: 92 AN: 43092

European-Finnish (FIN) AF: 0.00118 AC: 29 AN: 24574

Middle Eastern (MID) AF: 0.00152 AC: 3 AN: 1974

European-Non Finnish (NFE) AF: 0.000844 AC: 593 AN: 702530

Other (OTH) AF: 0.00166 AC: 50 AN: 30034

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00724 AC: 310 AN: 42846 Hom.: 0 Cov.: 0 AF XY: 0.00747 AC XY: 154 AN XY: 20626

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

African (AFR) AF: 0.00939 AC: 85 AN: 9048

American (AMR) AF: 0.00633 AC: 28 AN: 4424

Ashkenazi Jewish (ASJ) AF: 0.00643 AC: 5 AN: 778

East Asian (EAS) AF: 0.00927 AC: 12 AN: 1294

South Asian (SAS) AF: 0.00751 AC: 9 AN: 1198

European-Finnish (FIN) AF: 0.00998 AC: 26 AN: 2604

Middle Eastern (MID) AF: 0.0417 AC: 2 AN: 48

European-Non Finnish (NFE) AF: 0.00606 AC: 137 AN: 22608

Other (OTH) AF: 0.00530 AC: 3 AN: 566

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0592 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 18, 2015

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FMN2: BP4, BP7 -

FMN2-related disorder Benign:1

Jun 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.60
DANN	Benign	0.35
PhyloP100		-0.84
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: rs188083977; hg19: chr1-240370935; COSMIC: COSV60419915; COSMIC: COSV60419915;