14-52858372-C-T

Position:

• chr14-52858372-C-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.854

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FERMT2	NM_006832.3	c.*5G>A		3_prime_UTR_variant	15/15	ENST00000341590.8
LOC105370500	XR_943867.3	n.540-39701C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FERMT2	ENST00000341590.8	c.*5G>A		3_prime_UTR_variant	15/15	1	NM_006832.3	A1
	ENST00000654071.1	n.572-39701C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126333 AN: 152064 Hom.: 53208 Cov.: 32

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

GnomAD3 exomes AF: 0.866 AC: 217615 AN: 251242 Hom.: 94819 AF XY: 0.873 AC XY: 118578 AN XY: 135804

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 SAS exome AF: 0.871

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.: 32 AF XY: 0.889 AC XY: 645334 AN XY: 726218

Gnomad4 AFR exome AF: 0.680

Gnomad4 AMR exome AF: 0.840

Gnomad4 ASJ exome AF: 0.947

Gnomad4 EAS exome AF: 0.778

Gnomad4 SAS exome AF: 0.870

Gnomad4 FIN exome AF: 0.888

Gnomad4 NFE exome AF: 0.900

Gnomad4 OTH exome AF: 0.883

GnomAD4 genome AF: 0.831 AC: 126407 AN: 152182 Hom.: 53235 Cov.: 32 AF XY: 0.832 AC XY: 61926 AN XY: 74396

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.872

Gnomad4 ASJ AF: 0.953

Gnomad4 EAS AF: 0.795

Gnomad4 SAS AF: 0.860

Gnomad4 FIN AF: 0.887

Gnomad4 NFE AF: 0.896

Gnomad4 OTH AF: 0.862

Alfa AF: 0.866 Hom.: 31755

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.4
DANN	Benign	0.70

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: rs6572868; hg19: chr14-53325090;