rs4775501

Positions:

• chr15-62432826-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+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

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=-0.87).
• 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/exons	MANE	Protein	UniProt
TLN2	NM_015059.3	c.-238+42141C>T		intron_variant		ENST00000636159.2	NP_055874.2
TLN2	NM_001394547.1	c.-113+42141C>T		intron_variant			NP_001381476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLN2	ENST00000636159.2	c.-238+42141C>T		intron_variant		5	NM_015059.3	ENSP00000490662	P1
TLN2	ENST00000561322.1	n.160+42141C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.0659

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.0993

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.120

Alfa AF: 0.117 Hom.: 539

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4775501; hg19: chr15-62725025;