rs10491168

Variant names:

• chr17-63364102-A-G
• rs10491168
• NM_001394998.1:c.2582+8712A>G

Variant summary

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

The NM_001394998.1(TANC2):​c.2582+8712A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,174 control chromosomes in the GnomAD database, including 2,643 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 0.16 (2643 hom., cov: 32)
• Consequence: TANC2 NM_001394998.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170
• Publications: 3 publications found

Genes affected

TANC2 (HGNC:30212): (tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 2) Predicted to be involved in dense core granule cytoskeletal transport; regulation of dendritic spine development; and regulation of dendritic spine morphogenesis. Predicted to act upstream of or within in utero embryonic development. Located in dendritic spine. [provided by Alliance of Genome Resources, Apr 2022]

TANC2 Gene-Disease associations (from GenCC):

• intellectual developmental disorder with autistic features and language delay, with or without seizures

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: ClinGen, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394998.1. 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
	TANC2	NM_001394998.1	MANE Select	c.2582+8712A>G		intron	N/A	NP_001381927.1	A0A8I5KXR5
	TANC2	NM_001411076.1		c.2360+8712A>G		intron	N/A	NP_001398005.1	Q9HCD6-2
	TANC2	NM_025185.4		c.2360+8712A>G		intron	N/A	NP_079461.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANC2	ENST00000689528.1	MANE Select	c.2582+8712A>G		intron	N/A	ENSP00000510600.1	A0A8I5KXR5
	TANC2	ENST00000424789.6	TSL:1	c.2360+8712A>G		intron	N/A	ENSP00000387593.2	Q9HCD6-1
	TANC2	ENST00000583356.5	TSL:1	c.2144+8712A>G		intron	N/A	ENSP00000462109.1	J3KRP9

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24922 AN: 152056 Hom.: 2643 Cov.: 32

Gnomad AFR AF: 0.0432

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.0708

Gnomad SAS AF: 0.0760

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.164 AC: 24918 AN: 152174 Hom.: 2643 Cov.: 32 AF XY: 0.160 AC XY: 11933 AN XY: 74396

African (AFR) AF: 0.0431 AC: 1789 AN: 41528

American (AMR) AF: 0.144 AC: 2208 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 733 AN: 3470

East Asian (EAS) AF: 0.0706 AC: 366 AN: 5186

South Asian (SAS) AF: 0.0769 AC: 371 AN: 4822

European-Finnish (FIN) AF: 0.253 AC: 2676 AN: 10566

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16110 AN: 67992

Other (OTH) AF: 0.160 AC: 338 AN: 2110

Alfa AF: 0.205 Hom.: 449

Bravo AF: 0.150

Asia WGS AF: 0.0830 AC: 289 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.6
DANN	Benign	0.83
PhyloP100		0.017
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: rs10491168; hg19: chr17-61441463;