dbSNP rs3840006: INF2:c.2310+8delA (chr14-104711014-CA-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_022489.4(INF2):c.2310+8delA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27179 hom., cov: 0)

Exomes 𝑓: 0.56 ( 234135 hom. )

Consequence

INF2
NM_022489.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.665

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 14-104711014-CA-C is Benign according to our data. Variant chr14-104711014-CA-C is described in ClinVar as [Benign]. Clinvar id is 261606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-104711014-CA-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INF2	NM_022489.4 link	c.2310+8delA		splice_region_variant, intron_variant	Intron 14 of 22	ENST00000392634.9	NP_071934.3	Q27J81-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INF2	ENST00000392634.9 link	c.2310+8delA		splice_region_variant, intron_variant	Intron 14 of 22	5	NM_022489.4	ENSP00000376410.4		Q27J81-1

Frequencies

GnomAD3 genomes

AF:

0.593

AC:

90046

AN:

151950

Hom.:

27158

Cov.:

show subpopulations

Gnomad AFR

AF:

0.641

Gnomad AMI

AF:

0.531

Gnomad AMR

AF:

0.653

Gnomad ASJ

AF:

0.565

Gnomad EAS

AF:

0.914

Gnomad SAS

AF:

0.627

Gnomad FIN

AF:

0.537

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.532

Gnomad OTH

AF:

0.620

GnomAD3 exomes

AF:

0.607

AC:

148676

AN:

244882

Hom.:

46562

AF XY:

0.599

AC XY:

80076

AN XY:

133690

show subpopulations

Gnomad AFR exome

AF:

0.640

Gnomad AMR exome

AF:

0.704

Gnomad ASJ exome

AF:

0.570

Gnomad EAS exome

AF:

0.920

Gnomad SAS exome

AF:

0.618

Gnomad FIN exome

AF:

0.525

Gnomad NFE exome

AF:

0.540

Gnomad OTH exome

AF:

0.583

GnomAD4 exome

AF:

0.562

AC:

819702

AN:

1459118

Hom.:

234135

Cov.:

AF XY:

0.562

AC XY:

407783

AN XY:

725784

show subpopulations

Gnomad4 AFR exome

AF:

0.639

Gnomad4 AMR exome

AF:

0.695

Gnomad4 ASJ exome

AF:

0.572

Gnomad4 EAS exome

AF:

0.908

Gnomad4 SAS exome

AF:

0.616

Gnomad4 FIN exome

AF:

0.529

Gnomad4 NFE exome

AF:

0.538

Gnomad4 OTH exome

AF:

0.576

GnomAD4 genome

AF:

0.593

AC:

90110

AN:

152068

Hom.:

27179

Cov.:

AF XY:

0.597

AC XY:

44337

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.641

Gnomad4 AMR

AF:

0.653

Gnomad4 ASJ

AF:

0.565

Gnomad4 EAS

AF:

0.914

Gnomad4 SAS

AF:

0.625

Gnomad4 FIN

AF:

0.537

Gnomad4 NFE

AF:

0.532

Gnomad4 OTH

AF:

0.621

Alfa

AF:

0.440

Hom.:

2216

Bravo

AF:

0.606

Asia WGS

AF:

0.779

AC:

2705

AN:

3478

EpiCase

AF:

0.531

EpiControl

AF:

0.540

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

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

- -

Mar 18, 2021

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

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 90% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 84. Only high quality variants are reported. -

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

- -

not provided

Benign:1

Jun 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Focal segmental glomerulosclerosis

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over