14-52874727-G-T

Variant names:

• chr14-52874727-G-T
• rs7160582
• NM_006832.3:c.1098+496C>A

Variant summary

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

The NM_006832.3(FERMT2):​c.1098+496C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,112 control chromosomes in the GnomAD database, including 1,093 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 0.12 (1093 hom., cov: 32)
• Consequence: FERMT2 NM_006832.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.621

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]

ENSG00000285664 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FERMT2	NM_006832.3	c.1098+496C>A		intron_variant	Intron 8 of 14	ENST00000341590.8	NP_006823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FERMT2	ENST00000341590.8	c.1098+496C>A		intron_variant	Intron 8 of 14	1	NM_006832.3	ENSP00000340391.3

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17527 AN: 151996 Hom.: 1089 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0462

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.115 AC: 17551 AN: 152112 Hom.: 1093 Cov.: 32 AF XY: 0.116 AC XY: 8608 AN XY: 74364

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.0462

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0940 Hom.: 980

Bravo AF: 0.119

Asia WGS AF: 0.147 AC: 508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.0
DANN	Benign	0.42

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: rs7160582; hg19: chr14-53341445;