rs10133301

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022489.4(INF2):c.2640T>C(p.Asp880Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 1,612,146 control chromosomes in the GnomAD database, including 585,888 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.88 ( 59656 hom., cov: 35)

Exomes 𝑓: 0.85 ( 526232 hom. )

Consequence

INF2
NM_022489.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -2.25

Publications

25 publications found

Variant links:

Genes affected

INF2 (HGNC:23791): (inverted formin 2) This gene represents a member of the formin family of proteins. It is considered a diaphanous formin due to the presence of a diaphanous inhibitory domain located at the N-terminus of the encoded protein. Studies of a similar mouse protein indicate that the protein encoded by this locus may function in polymerization and depolymerization of actin filaments. Mutations at this locus have been associated with focal segmental glomerulosclerosis 5.[provided by RefSeq, Aug 2010]

INF2 Gene-Disease associations (from GenCC):

Charcot-Marie-Tooth disease dominant intermediate E
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
focal segmental glomerulosclerosis 5
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
familial idiopathic steroid-resistant nephrotic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

INF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 14-104712857-T-C is Benign according to our data. Variant chr14-104712857-T-C is described in ClinVar as Benign. ClinVar VariationId is 261611.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INF2	NM_022489.4 link	c.2640T>C	p.Asp880Asp	synonymous_variant	Exon 18 of 23	ENST00000392634.9	NP_071934.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INF2	ENST00000392634.9 link	c.2640T>C	p.Asp880Asp	synonymous_variant	Exon 18 of 23	5	NM_022489.4	ENSP00000376410.4

Frequencies

GnomAD3 genomes

AF:

0.882

AC:

134253

AN:

152184

Hom.:

59598

Cov.:

show subpopulations

Gnomad AFR

AF:

0.971

Gnomad AMI

AF:

0.789

Gnomad AMR

AF:

0.901

Gnomad ASJ

AF:

0.903

Gnomad EAS

AF:

0.942

Gnomad SAS

AF:

0.816

Gnomad FIN

AF:

0.789

Gnomad MID

AF:

0.911

Gnomad NFE

AF:

0.838

Gnomad OTH

AF:

0.902

GnomAD2 exomes

AF:

0.861

AC:

212235

AN:

246426

AF XY:

0.855

show subpopulations

Gnomad AFR exome

AF:

0.975

Gnomad AMR exome

AF:

0.901

Gnomad ASJ exome

AF:

0.905

Gnomad EAS exome

AF:

0.948

Gnomad FIN exome

AF:

0.785

Gnomad NFE exome

AF:

0.841

Gnomad OTH exome

AF:

0.871

GnomAD4 exome

AF:

0.848

AC:

1238245

AN:

1459844

Hom.:

526232

Cov.:

AF XY:

0.847

AC XY:

615049

AN XY:

726154

show subpopulations

African (AFR)

AF:

0.977

AC:

32712

AN:

33470

American (AMR)

AF:

0.902

AC:

40286

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.904

AC:

23600

AN:

26110

East Asian (EAS)

AF:

0.939

AC:

37252

AN:

39682

South Asian (SAS)

AF:

0.819

AC:

70635

AN:

86236

European-Finnish (FIN)

AF:

0.787

AC:

41036

AN:

52112

Middle Eastern (MID)

AF:

0.893

AC:

5150

AN:

5766

European-Non Finnish (NFE)

AF:

0.842

AC:

935381

AN:

1111468

Other (OTH)

AF:

0.865

AC:

52193

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

11356

22712

34069

45425

56781

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21146

42292

63438

84584

105730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.882

AC:

134368

AN:

152302

Hom.:

59656

Cov.:

AF XY:

0.880

AC XY:

65550

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.972

AC:

40412

AN:

41596

American (AMR)

AF:

0.901

AC:

13786

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.903

AC:

3135

AN:

3472

East Asian (EAS)

AF:

0.942

AC:

4878

AN:

5178

South Asian (SAS)

AF:

0.814

AC:

3935

AN:

4832

European-Finnish (FIN)

AF:

0.789

AC:

8362

AN:

10602

Middle Eastern (MID)

AF:

0.908

AC:

267

AN:

294

European-Non Finnish (NFE)

AF:

0.838

AC:

56963

AN:

67998

Other (OTH)

AF:

0.903

AC:

1910

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

826

1652

2478

3304

4130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.857

Hom.:

86174

Bravo

AF:

0.897

Asia WGS

AF:

0.912

AC:

3168

AN:

3476

EpiCase

AF:

0.843

EpiControl

AF:

0.855

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 99% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 92. Only high quality variants are reported.

Dec 21, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Apr 25, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Focal segmental glomerulosclerosis 5;C4302667:Charcot-Marie-Tooth disease dominant intermediate E

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Charcot-Marie-Tooth disease dominant intermediate E

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Focal segmental glomerulosclerosis 5

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.23

(source)

DANN

Benign

0.23

PhyloP100

-2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over