15-62403872-C-T

Variant names:

• chr15-62403872-C-T
• rs290297
• NM_015059.3:c.-238+13187C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015059.3(TLN2):​c.-238+13187C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.882 in 152,212 control chromosomes in the GnomAD database, including 60,879 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 0.88 (60879 hom., cov: 32)
• Consequence: TLN2 NM_015059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLN2	NM_015059.3	c.-238+13187C>T		intron_variant	Intron 1 of 58	ENST00000636159.2	NP_055874.2
TLN2	NM_001394547.1	c.-113+13187C>T		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.-238+13187C>T		intron_variant	Intron 1 of 58	5	NM_015059.3	ENSP00000490662.2
TLN2	ENST00000561322.1	n.160+13187C>T		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.882 AC: 134207 AN: 152094 Hom.: 60837 Cov.: 32

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.984

Gnomad AMR AF: 0.943

Gnomad ASJ AF: 0.984

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.987

Gnomad FIN AF: 0.982

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.973

Gnomad OTH AF: 0.910

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

GnomAD4 genome AF: 0.882 AC: 134303 AN: 152212 Hom.: 60879 Cov.: 32 AF XY: 0.886 AC XY: 65912 AN XY: 74428

African (AFR) AF: 0.646 AC: 26792 AN: 41476

American (AMR) AF: 0.943 AC: 14435 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.984 AC: 3418 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5169 AN: 5174

South Asian (SAS) AF: 0.987 AC: 4762 AN: 4826

European-Finnish (FIN) AF: 0.982 AC: 10420 AN: 10612

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.973 AC: 66204 AN: 68034

Other (OTH) AF: 0.911 AC: 1923 AN: 2112

Alfa AF: 0.932 Hom.: 13919

Bravo AF: 0.867

Asia WGS AF: 0.968 AC: 3366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.93
DANN	Benign	0.82
PhyloP100		-0.30

Splicing

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

Other links and lift over

dbSNP: rs290297; hg19: chr15-62696071;