14-104713451-A-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022489.4(INF2):c.2885A>G(p.Lys962Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K962T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

INF2
NM_022489.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.622

Publications

1 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: 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 (MetaRNN=0.057798564).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022489.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
INF2	NM_022489.4	MANE Select	c.2885A>G	p.Lys962Arg	missense	Exon 20 of 23	NP_071934.3
INF2	NM_001426862.1		c.2885A>G	p.Lys962Arg	missense	Exon 20 of 23	NP_001413791.1
INF2	NM_001426863.1		c.2885A>G	p.Lys962Arg	missense	Exon 20 of 23	NP_001413792.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
INF2	ENST00000392634.9	TSL:5 MANE Select	c.2885A>G	p.Lys962Arg	missense	Exon 20 of 23	ENSP00000376410.4
INF2	ENST00000617571.5	TSL:1	n.2881A>G		splice_region non_coding_transcript_exon	Exon 19 of 22	ENSP00000483829.2
INF2	ENST00000675207.1		c.2981A>G	p.Lys994Arg	missense	Exon 20 of 23	ENSP00000502644.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000827

AC:

AN:

241914

AF XY:

0.00000757

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458306

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725168

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33438

American (AMR)

AF:

0.00

AC:

AN:

44448

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26014

East Asian (EAS)

AF:

0.00

AC:

AN:

39644

South Asian (SAS)

AF:

0.00

AC:

AN:

85638

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52038

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111056

Other (OTH)

AF:

0.00

AC:

AN:

60270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000829

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.044

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.66

M_CAP

Benign

0.046

MetaRNN

Benign

0.058

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.88

PhyloP100

0.62

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.6

REVEL

Benign

0.17

Sift

Benign

0.16

Sift4G

Benign

0.27

Polyphen

0.040

Vest4

0.053

MutPred

0.28

Gain of catalytic residue at G963 (P = 0.0062)

MVP

0.21

MPC

0.20

ClinPred

0.13

GERP RS

-3.1

Varity_R

0.065

gMVP

0.29

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over