rs8008270

Positions:

• chr14-52905612-T-C
• chr14-52905612-T-G

Variant summary

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

The NM_006832.3(FERMT2):​c.392-12185A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,044 control chromosomes in the GnomAD database, including 48,898 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 0.80 (48898 hom., cov: 30)
• Consequence: FERMT2 NM_006832.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.952

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FERMT2	NM_006832.3	c.392-12185A>G		intron_variant		ENST00000341590.8
LOC105370500	XR_943867.3	n.621+7458T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FERMT2	ENST00000341590.8	c.392-12185A>G		intron_variant		1	NM_006832.3	A1
	ENST00000654071.1	n.653+7458T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121509 AN: 151926 Hom.: 48868 Cov.: 30

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.903

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.729

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.806

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

GnomAD4 genome AF: 0.800 AC: 121591 AN: 152044 Hom.: 48898 Cov.: 30 AF XY: 0.805 AC XY: 59831 AN XY: 74300

Gnomad4 AFR AF: 0.718

Gnomad4 AMR AF: 0.857

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.902

Gnomad4 FIN AF: 0.845

Gnomad4 NFE AF: 0.810

Gnomad4 OTH AF: 0.808

Alfa AF: 0.812 Hom.: 98682

Bravo AF: 0.796

Asia WGS AF: 0.932 AC: 3240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.19
DANN	Benign	0.25

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: rs8008270; hg19: chr14-53372330;