14-52922981-T-C

Position:

• chr14-52922981-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.158-3625A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,238 control chromosomes in the GnomAD database, including 1,304 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 0.13 (1304 hom., cov: 32)
• Consequence: FERMT2 NM_006832.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.742

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FERMT2	NM_006832.3	c.158-3625A>G		intron_variant		ENST00000341590.8
LOC105370500	XR_943867.3	n.622-5376T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FERMT2	ENST00000341590.8	c.158-3625A>G		intron_variant		1	NM_006832.3	A1
	ENST00000654071.1	n.740+1305T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19420 AN: 152120 Hom.: 1304 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.0889

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0880

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.128 AC: 19445 AN: 152238 Hom.: 1304 Cov.: 32 AF XY: 0.125 AC XY: 9293 AN XY: 74426

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.0887

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0893

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.137

Alfa AF: 0.138 Hom.: 348

Bravo AF: 0.125

Asia WGS AF: 0.0510 AC: 180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.7
DANN	Benign	0.69

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: rs62003539; hg19: chr14-53389699;