15-62422843-C-T

Position:

• chr15-62422843-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLN2	NM_015059.3	c.-238+32158C>T		intron_variant		ENST00000636159.2	NP_055874.2
TLN2	NM_001394547.1	c.-113+32158C>T		intron_variant			NP_001381476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLN2	ENST00000636159.2	c.-238+32158C>T		intron_variant		5	NM_015059.3	ENSP00000490662	P1
TLN2	ENST00000561322.1	n.160+32158C>T		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.0930

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.218

Alfa AF: 0.210 Hom.: 3417

Bravo AF: 0.220

Asia WGS AF: 0.478 AC: 1662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2456936; hg19: chr15-62715042;