Genetic Variant FERMT2:c.158-14555A>G (chr14-52933911-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006832.3(FERMT2):c.158-14555A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0878 in 152,008 control chromosomes in the GnomAD database, including 677 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.088 ( 677 hom., cov: 31)

Consequence

FERMT2
NM_006832.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.64

Publications

124 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006832.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FERMT2	NM_006832.3	MANE Select	c.158-14555A>G	intron	N/A	NP_006823.1	Q96AC1-1
FERMT2	NM_001134999.2		c.158-14555A>G	intron	N/A	NP_001128471.1	Q96AC1-3
FERMT2	NM_001135000.2		c.158-14555A>G	intron	N/A	NP_001128472.1	Q96AC1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FERMT2	ENST00000341590.8	TSL:1 MANE Select	c.158-14555A>G	intron	N/A	ENSP00000340391.3	Q96AC1-1
FERMT2	ENST00000553373.5	TSL:1	c.158-14555A>G	intron	N/A	ENSP00000451084.1	Q96AC1-3
FERMT2	ENST00000395631.6	TSL:1	c.158-14555A>G	intron	N/A	ENSP00000378993.2	Q96AC1-1

Frequencies

GnomAD3 genomes

AF:

0.0878

AC:

13329

AN:

151892

Hom.:

676

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0622

Gnomad AMI

AF:

0.0220

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.0413

Gnomad EAS

AF:

0.206

Gnomad SAS

AF:

0.115

Gnomad FIN

AF:

0.0941

Gnomad MID

AF:

0.0446

Gnomad NFE

AF:

0.0923

Gnomad OTH

AF:

0.0763

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0878

AC:

13339

AN:

152008

Hom.:

677

Cov.:

AF XY:

0.0892

AC XY:

6623

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.0622

AC:

2581

AN:

41480

American (AMR)

AF:

0.101

AC:

1544

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.0413

AC:

143

AN:

3466

East Asian (EAS)

AF:

0.206

AC:

1059

AN:

5150

South Asian (SAS)

AF:

0.115

AC:

551

AN:

4806

European-Finnish (FIN)

AF:

0.0941

AC:

995

AN:

10570

Middle Eastern (MID)

AF:

0.0445

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0923

AC:

6273

AN:

67966

Other (OTH)

AF:

0.0760

AC:

160

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

583

1166

1748

2331

2914

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<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:

0.0917

Hom.:

2461

Bravo

AF:

0.0907

Asia WGS

AF:

0.139

AC:

480

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

1.6

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over