chr15-62512289-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.695 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.-237-77398T>C		intron	N/A	NP_055874.2	Q9Y4G6
	TLN2	NM_001394547.1		c.-112-77398T>C		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.-237-77398T>C		intron	N/A	ENSP00000490662.2	Q9Y4G6
	TLN2	ENST00000895916.1		c.-112-77398T>C		intron	N/A	ENSP00000565975.1
	TLN2	ENST00000964497.1		c.-193-44209T>C		intron	N/A	ENSP00000634556.1

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

African (AFR) AF: 0.701 AC: 29005 AN: 41360

American (AMR) AF: 0.472 AC: 7197 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1206 AN: 3468

East Asian (EAS) AF: 0.576 AC: 2968 AN: 5150

South Asian (SAS) AF: 0.445 AC: 2129 AN: 4788

European-Finnish (FIN) AF: 0.380 AC: 4009 AN: 10554

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27496 AN: 67924

Other (OTH) AF: 0.478 AC: 1005 AN: 2102

Alfa AF: 0.435 Hom.: 40397

Bravo AF: 0.511

Asia WGS AF: 0.510 AC: 1770 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.33
PhyloP100		-0.28

Splicing

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

Other links and lift over

dbSNP: rs448458; hg19: chr15-62804488;