rs4775501

Variant names:

• chr15-62432826-C-T
• rs4775501
• NM_015059.3:c.-238+42141C>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+42141C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,028 control chromosomes in the GnomAD database, including 1,032 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 0.11 (1032 hom., cov: 32)
• Consequence: TLN2 NM_015059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLN2	NM_015059.3	c.-238+42141C>T		intron_variant	Intron 1 of 58	ENST00000636159.2	NP_055874.2
TLN2	NM_001394547.1	c.-113+42141C>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+42141C>T		intron_variant	Intron 1 of 58	5	NM_015059.3	ENSP00000490662.2
TLN2	ENST00000561322.1	n.160+42141C>T		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16598 AN: 151910 Hom.: 1033 Cov.: 32

Gnomad AFR AF: 0.0660

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.0994

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.109 AC: 16602 AN: 152028 Hom.: 1032 Cov.: 32 AF XY: 0.110 AC XY: 8183 AN XY: 74296

African (AFR) AF: 0.0659 AC: 2733 AN: 41466

American (AMR) AF: 0.151 AC: 2313 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 409 AN: 3472

East Asian (EAS) AF: 0.0993 AC: 511 AN: 5148

South Asian (SAS) AF: 0.115 AC: 555 AN: 4810

European-Finnish (FIN) AF: 0.125 AC: 1323 AN: 10564

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8366 AN: 67974

Other (OTH) AF: 0.120 AC: 254 AN: 2112

Alfa AF: 0.118 Hom.: 597

Bravo AF: 0.108

Asia WGS AF: 0.128 AC: 443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.8
DANN	Benign	0.65
PhyloP100		-0.38

Splicing

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

Other links and lift over

dbSNP: rs4775501; hg19: chr15-62725025;