ENST00000553373.5:c.1612A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000553373.5(FERMT2):c.1612A>G(p.Ile538Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000239 in 1,520,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

FERMT2
ENST00000553373.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.171

Publications

1 publications found

Variant links:

Genes affected

FERMT2 (HGNC:15767): (FERM domain containing kindlin 2) Enables several functions, including actin binding activity; phosphatidylinositol-3,4,5-trisphosphate binding activity; and type I transforming growth factor beta receptor binding activity. Involved in several processes, including cell surface receptor signaling pathway; positive regulation of cell differentiation; and positive regulation of cellular component biogenesis. Acts upstream of or within cell adhesion and protein localization to cell junction. Located in cytosol; focal adhesion; and nucleoplasm. Is extrinsic component of cytoplasmic side of plasma membrane. Part of adherens junction and plasma membrane. Biomarker of acute myeloid leukemia. [provided by Alliance of Genome Resources, Apr 2022]

FERMT2 links:

ENSG00000285664 (HGNC:):

ENSG00000285664 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004634112).

BP6

Variant 14-52861025-T-C is Benign according to our data. Variant chr14-52861025-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2400674.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 213 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FERMT2	NM_006832.3 link	c.1603-560A>G		intron_variant	Intron 12 of 14	ENST00000341590.8	NP_006823.1	Q96AC1-1A0A024R687

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FERMT2	ENST00000341590.8 link	c.1603-560A>G		intron_variant	Intron 12 of 14	1	NM_006832.3	ENSP00000340391.3		Q96AC1-1

Frequencies

GnomAD3 genomes

AF:

0.00140

AC:

212

AN:

151838

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00499

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000264

AC:

AN:

125128

AF XY:

0.000225

show subpopulations

Gnomad AFR exome

AF:

0.00428

Gnomad AMR exome

AF:

0.000305

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000110

AC:

151

AN:

1368124

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

673862

show subpopulations

African (AFR)

AF:

0.00442

AC:

130

AN:

29444

American (AMR)

AF:

0.000246

AC:

AN:

28420

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24580

East Asian (EAS)

AF:

0.00

AC:

AN:

34218

South Asian (SAS)

AF:

0.0000141

AC:

AN:

71106

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49034

Middle Eastern (MID)

AF:

0.000177

AC:

AN:

5638

European-Non Finnish (NFE)

AF:

0.00000187

AC:

AN:

1068940

Other (OTH)

AF:

0.000176

AC:

AN:

56744

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00140

AC:

213

AN:

151956

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.00500

AC:

207

AN:

41418

American (AMR)

AF:

0.000131

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67986

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00160

Hom.:

Bravo

AF:

0.00148

ESP6500AA

AF:

0.00723

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000363

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 18, 2021

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.75

CADD

Benign

5.9

(source)

DANN

Benign

0.47

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.56

T;T;.;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.0046

T;T;T;T

MetaSVM

Benign

-1.0

PhyloP100

-0.17

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.040

N;N;N;N

REVEL

Benign

0.050

Sift

Benign

0.95

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

.;.;.;B

Vest4

0.097, 0.096, 0.12

MVP

0.17

MPC

0.33

ClinPred

0.0014

GERP RS

-3.0

gMVP

0.19

Mutation Taster

=100/0

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

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ENST00000553373.5:c.1612A>G

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