Genetic Variant FERMT2:c.*5G>A (chr14-52858372-C-T) – 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.*5G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 1,611,796 control chromosomes in the GnomAD database, including 630,318 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 0.83 ( 53235 hom., cov: 32)

Exomes 𝑓: 0.89 ( 577083 hom. )

Consequence

FERMT2
NM_006832.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.854

Publications

17 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

new If you want to explore the variant's impact on the transcript NM_006832.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.89 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FERMT2	NM_006832.3	MANE Select	c.*5G>A		3_prime_UTR	Exon 15 of 15	NP_006823.1	Q96AC1-1
	FERMT2	NM_001134999.2		c.*5G>A		3_prime_UTR	Exon 16 of 16	NP_001128471.1	Q96AC1-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FERMT2	ENST00000341590.8	TSL:1 MANE Select	c.*5G>A	3_prime_UTR	Exon 15 of 15	ENSP00000340391.3	Q96AC1-1
FERMT2	ENST00000395631.6	TSL:1	c.*5G>A	3_prime_UTR	Exon 15 of 15	ENSP00000378993.2	Q96AC1-1
FERMT2	ENST00000875235.1		c.*5G>A	3_prime_UTR	Exon 16 of 16	ENSP00000545294.1

Frequencies

GnomAD3 genomes

AF:

0.831

AC:

126333

AN:

152064

Hom.:

53208

Cov.:

show subpopulations

Gnomad AFR

AF:

0.681

Gnomad AMI

AF:

0.910

Gnomad AMR

AF:

0.872

Gnomad ASJ

AF:

0.953

Gnomad EAS

AF:

0.795

Gnomad SAS

AF:

0.860

Gnomad FIN

AF:

0.887

Gnomad MID

AF:

0.883

Gnomad NFE

AF:

0.896

Gnomad OTH

AF:

0.861

GnomAD2 exomes

AF:

0.866

AC:

217615

AN:

251242

AF XY:

0.873

show subpopulations

Gnomad AFR exome

AF:

0.677

Gnomad AMR exome

AF:

0.835

Gnomad ASJ exome

AF:

0.946

Gnomad EAS exome

AF:

0.792

Gnomad FIN exome

AF:

0.887

Gnomad NFE exome

AF:

0.901

Gnomad OTH exome

AF:

0.895

GnomAD4 exome

AF:

0.888

AC:

1296225

AN:

1459614

Hom.:

577083

Cov.:

AF XY:

0.889

AC XY:

645334

AN XY:

726218

show subpopulations

African (AFR)

AF:

0.680

AC:

22722

AN:

33426

American (AMR)

AF:

0.840

AC:

37575

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.947

AC:

24741

AN:

26118

East Asian (EAS)

AF:

0.778

AC:

30855

AN:

39672

South Asian (SAS)

AF:

0.870

AC:

75019

AN:

86190

European-Finnish (FIN)

AF:

0.888

AC:

47434

AN:

53406

Middle Eastern (MID)

AF:

0.908

AC:

5235

AN:

5766

European-Non Finnish (NFE)

AF:

0.900

AC:

999361

AN:

1110014

Other (OTH)

AF:

0.883

AC:

53283

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

6870

13739

20609

27478

34348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21370

42740

64110

85480

106850

<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:

0.831

AC:

126407

AN:

152182

Hom.:

53235

Cov.:

AF XY:

0.832

AC XY:

61926

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.681

AC:

28263

AN:

41478

American (AMR)

AF:

0.872

AC:

13332

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.953

AC:

3308

AN:

3472

East Asian (EAS)

AF:

0.795

AC:

4120

AN:

5182

South Asian (SAS)

AF:

0.860

AC:

4152

AN:

4828

European-Finnish (FIN)

AF:

0.887

AC:

9389

AN:

10584

Middle Eastern (MID)

AF:

0.878

AC:

258

AN:

294

European-Non Finnish (NFE)

AF:

0.896

AC:

60933

AN:

68022

Other (OTH)

AF:

0.862

AC:

1822

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1031

2063

3094

4126

5157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

876

1752

2628

3504

4380

<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:

0.866

Hom.:

36162

Bravo

AF:

0.820

Asia WGS

AF:

0.833

AC:

2898

AN:

3478

EpiCase

AF:

0.901

EpiControl

AF:

0.907

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

8.4

(source)

DANN

Benign

0.70

PhyloP100

0.85

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over