rs7182961

chr15-62628393-C-G

Variant summary

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

The NM_015059.3(TLN2):c.-37+9918C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,194 control chromosomes in the GnomAD database, including 5,077 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 0.23 (5077 hom., cov: 34)
• Consequence: TLN2 NM_015059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLN2	NM_015059.3	c.-37+9918C>G		intron_variant		ENST00000636159.2
TLN2	NM_001394547.1	c.-36-18882C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLN2	ENST00000636159.2	c.-37+9918C>G		intron_variant		5	NM_015059.3	P1
TLN2	ENST00000561311.5	c.-36-18882C>G		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34253 AN: 152076 Hom.: 5073 Cov.: 34

Gnomad AFR AF: 0.0621

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.225 AC: 34261 AN: 152194 Hom.: 5077 Cov.: 34 AF XY: 0.234 AC XY: 17398 AN XY: 74386

Gnomad4 AFR AF: 0.0619

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.228

Alfa AF: 0.250 Hom.: 733

Bravo AF: 0.212

Asia WGS AF: 0.426 AC: 1480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.3
Dann	Benign	0.46

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: rs7182961; hg19: chr15-62920592;