15-62670095-C-T

Variant names:

• chr15-62670095-C-T
• rs1574119
• NM_015059.3:c.789-3732C>T

Variant summary

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

The NM_015059.3(TLN2):​c.789-3732C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 151,998 control chromosomes in the GnomAD database, including 7,403 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 0.30 (7403 hom., cov: 32)
• Consequence: TLN2 NM_015059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127

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]

LOC105370855 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLN2	NM_015059.3	c.789-3732C>T		intron_variant	Intron 9 of 58	ENST00000636159.2	NP_055874.2
TLN2	NM_001394547.1	c.789-3732C>T		intron_variant	Intron 8 of 57		NP_001381476.1
LOC105370855	XR_007064672.1	n.461-1023G>A		intron_variant	Intron 2 of 3
LOC105370855	XR_007064673.1	n.530-1023G>A		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLN2	ENST00000636159.2	c.789-3732C>T		intron_variant	Intron 9 of 58	5	NM_015059.3	ENSP00000490662.2
TLN2	ENST00000561311.5	c.789-3732C>T		intron_variant	Intron 8 of 57	5		ENSP00000453508.1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45844 AN: 151878 Hom.: 7394 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.302 AC: 45879 AN: 151998 Hom.: 7403 Cov.: 32 AF XY: 0.304 AC XY: 22586 AN XY: 74294

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.645

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.284

Alfa AF: 0.275 Hom.: 2860

Bravo AF: 0.305

Asia WGS AF: 0.437 AC: 1518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.38

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: rs1574119; hg19: chr15-62962294;