rs2025453

Variant names:

• chr10-96471692-A-C
• rs2025453
• NM_012465.4:c.286+8657T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-96471692-A-C
• chr10-96471692-A-T

Variant summary

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

The NM_012465.4(TLL2):​c.286+8657T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,094 control chromosomes in the GnomAD database, including 46,548 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 0.78 (46548 hom., cov: 31)
• Consequence: TLL2 NM_012465.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.125
• Publications: 1 publications found

Genes affected

TLL2 (HGNC:11844): (tolloid like 2) This gene encodes an astacin-like zinc-dependent metalloprotease and is a subfamily member of the metzincin family. Unlike other family members, a similar protein in mice does not cleave procollagen C-propeptides or chordin. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLL2	NM_012465.4	c.286+8657T>G		intron_variant	Intron 2 of 20	ENST00000357947.4	NP_036597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLL2	ENST00000357947.4	c.286+8657T>G		intron_variant	Intron 2 of 20	1	NM_012465.4	ENSP00000350630.3
TLL2	ENST00000469598.1	n.519+8657T>G		intron_variant	Intron 2 of 12	2

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118563 AN: 151976 Hom.: 46507 Cov.: 31

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.798

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

GnomAD4 genome AF: 0.780 AC: 118660 AN: 152094 Hom.: 46548 Cov.: 31 AF XY: 0.777 AC XY: 57811 AN XY: 74358

African (AFR) AF: 0.844 AC: 35011 AN: 41488

American (AMR) AF: 0.813 AC: 12430 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.774 AC: 2684 AN: 3468

East Asian (EAS) AF: 0.911 AC: 4712 AN: 5174

South Asian (SAS) AF: 0.812 AC: 3910 AN: 4818

European-Finnish (FIN) AF: 0.678 AC: 7158 AN: 10560

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.738 AC: 50165 AN: 67988

Other (OTH) AF: 0.800 AC: 1688 AN: 2110

Alfa AF: 0.757 Hom.: 41135

Bravo AF: 0.797

Asia WGS AF: 0.861 AC: 2993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	8.4
DANN	Benign	0.44
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2025453; hg19: chr10-98231449;