NM_006832.3:c.392-12185A>G

Variant names:

• chr14-52905612-T-C
• rs8008270
• NM_006832.3:c.392-12185A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 53 publications found

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]

LOC105370500 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FERMT2	NM_006832.3	c.392-12185A>G		intron_variant	Intron 3 of 14	ENST00000341590.8	NP_006823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FERMT2	ENST00000341590.8	c.392-12185A>G		intron_variant	Intron 3 of 14	1	NM_006832.3	ENSP00000340391.3

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

African (AFR) AF: 0.718 AC: 29784 AN: 41472

American (AMR) AF: 0.857 AC: 13079 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2612 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5167 AN: 5170

South Asian (SAS) AF: 0.902 AC: 4336 AN: 4808

European-Finnish (FIN) AF: 0.845 AC: 8925 AN: 10560

Middle Eastern (MID) AF: 0.736 AC: 215 AN: 292

European-Non Finnish (NFE) AF: 0.810 AC: 55094 AN: 67976

Other (OTH) AF: 0.808 AC: 1706 AN: 2112

Alfa AF: 0.808 Hom.: 207142

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
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8008270; hg19: chr14-53372330;