rs17125944

Positions:

• chr14-52933911-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FERMT2	NM_006832.3	c.158-14555A>G		intron_variant		ENST00000341590.8	NP_006823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FERMT2	ENST00000341590.8	c.158-14555A>G		intron_variant		1	NM_006832.3	ENSP00000340391.3

Frequencies

GnomAD3 genomes AF: 0.0878 AC: 13329 AN: 151892 Hom.: 676 Cov.: 31

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.: 31 AF XY: 0.0892 AC XY: 6623 AN XY: 74284

Gnomad4 AFR AF: 0.0622

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0413

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0941

Gnomad4 NFE AF: 0.0923

Gnomad4 OTH AF: 0.0760

Alfa AF: 0.0890 Hom.: 982

Bravo AF: 0.0907

Asia WGS AF: 0.139 AC: 480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.80

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

LitVar

Other links and lift over

dbSNP: rs17125944; hg19: chr14-53400629;