chr15-62422843-C-T

Variant names:

• chr15-62422843-C-T
• rs2456936
• NM_015059.3:c.-238+32158C>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+32158C>T 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 152,148 control chromosomes in the GnomAD database, including 5,020 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 (5020 hom., cov: 32)
• Consequence: TLN2 NM_015059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179
• Publications: 5 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 (EAS) allele frequency at 95% confidence interval = 0.632 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.-238+32158C>T		intron	N/A	NP_055874.2	Q9Y4G6
	TLN2	NM_001394547.1		c.-113+32158C>T		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.-238+32158C>T		intron	N/A	ENSP00000490662.2	Q9Y4G6
	TLN2	ENST00000895916.1		c.-113+32158C>T		intron	N/A	ENSP00000565975.1
	TLN2	ENST00000964497.1		c.-194+32158C>T		intron	N/A	ENSP00000634556.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34252 AN: 152030 Hom.: 5018 Cov.: 32

Gnomad AFR AF: 0.0931

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.225 AC: 34266 AN: 152148 Hom.: 5020 Cov.: 32 AF XY: 0.239 AC XY: 17768 AN XY: 74380

African (AFR) AF: 0.0930 AC: 3863 AN: 41520

American (AMR) AF: 0.338 AC: 5166 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 784 AN: 3468

East Asian (EAS) AF: 0.650 AC: 3352 AN: 5158

South Asian (SAS) AF: 0.441 AC: 2126 AN: 4816

European-Finnish (FIN) AF: 0.313 AC: 3310 AN: 10584

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15018 AN: 67996

Other (OTH) AF: 0.218 AC: 460 AN: 2110

Alfa AF: 0.218 Hom.: 5725

Bravo AF: 0.220

Asia WGS AF: 0.478 AC: 1662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.38
PhyloP100		-0.18

Splicing

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

Other links and lift over

dbSNP: rs2456936; hg19: chr15-62715042;