15-62512289-T-C

Variant names:

• chr15-62512289-T-C
• rs448458
• NM_015059.3:c.-237-77398T>C

Variant summary

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

The NM_015059.3(TLN2):​c.-237-77398T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 151,802 control chromosomes in the GnomAD database, including 20,055 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 0.50 (20055 hom., cov: 31)
• Consequence: TLN2 NM_015059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280

Genes affected

TLN2 (HGNC:15447): (talin 2) This gene encodes a protein related to talin 1, a cytoskeletal protein that plays a significant role in the assembly of actin filaments and in spreading and migration of various cell types, including fibroblasts and osteoclasts. This protein has a different pattern of expression compared to talin 1 but, like talin 1, is thought to associate with unique transmembrane receptors to form novel linkages between extracellular matrices and the actin cytoskeleton. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLN2	NM_015059.3	c.-237-77398T>C		intron_variant	Intron 1 of 58	ENST00000636159.2	NP_055874.2
TLN2	NM_001394547.1	c.-112-77398T>C		intron_variant	Intron 1 of 57		NP_001381476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLN2	ENST00000636159.2	c.-237-77398T>C		intron_variant	Intron 1 of 58	5	NM_015059.3	ENSP00000490662.2
TLN2	ENST00000561197.5	n.150+58548T>C		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75299 AN: 151682 Hom.: 20009 Cov.: 31

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.497 AC: 75408 AN: 151802 Hom.: 20055 Cov.: 31 AF XY: 0.495 AC XY: 36690 AN XY: 74168

Gnomad4 AFR AF: 0.701

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.576

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.478

Alfa AF: 0.413 Hom.: 20963

Bravo AF: 0.511

Asia WGS AF: 0.510 AC: 1770 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs448458; hg19: chr15-62804488;