rs7182961

Variant names:

• chr15-62628393-C-G
• rs7182961
• NM_015059.3:c.-37+9918C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

TLN2 Gene-Disease associations (from GenCC):

• camptodactyly of fingers

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015059.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLN2	NM_015059.3	MANE Select	c.-37+9918C>G		intron	N/A	NP_055874.2	Q9Y4G6
	TLN2	NM_001394547.1		c.-36-18882C>G		intron	N/A	NP_001381476.1	Q9Y4G6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLN2	ENST00000636159.2	TSL:5 MANE Select	c.-37+9918C>G		intron	N/A	ENSP00000490662.2	Q9Y4G6
	TLN2	ENST00000561311.5	TSL:5	c.-36-18882C>G		intron	N/A	ENSP00000453508.1	Q9Y4G6
	TLN2	ENST00000895916.1		c.-36-18882C>G		intron	N/A	ENSP00000565975.1

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

African (AFR) AF: 0.0619 AC: 2573 AN: 41536

American (AMR) AF: 0.260 AC: 3972 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 752 AN: 3470

East Asian (EAS) AF: 0.640 AC: 3309 AN: 5170

South Asian (SAS) AF: 0.360 AC: 1734 AN: 4822

European-Finnish (FIN) AF: 0.333 AC: 3517 AN: 10570

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17651 AN: 68014

Other (OTH) AF: 0.228 AC: 482 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.3
DANN	Benign	0.46
PhyloP100		1.6
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: rs7182961; hg19: chr15-62920592;