chr17-63349337-C-T

Variant names:

• chr17-63349337-C-T
• rs10491167
• NM_001394998.1:c.1808-1913C>T

Variant summary

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

The NM_001394998.1(TANC2):​c.1808-1913C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,088 control chromosomes in the GnomAD database, including 2,807 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 0.18 (2807 hom., cov: 32)
• Consequence: TANC2 NM_001394998.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.656
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.235 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.1808-1913C>T		intron	N/A	NP_001381927.1	A0A8I5KXR5
	TANC2	NM_001411076.1		c.1586-1913C>T		intron	N/A	NP_001398005.1	Q9HCD6-2
	TANC2	NM_025185.4		c.1586-1913C>T		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.1808-1913C>T		intron	N/A	ENSP00000510600.1	A0A8I5KXR5
	TANC2	ENST00000424789.6	TSL:1	c.1586-1913C>T		intron	N/A	ENSP00000387593.2	Q9HCD6-1
	TANC2	ENST00000583356.5	TSL:1	c.1370-1913C>T		intron	N/A	ENSP00000462109.1	J3KRP9

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27182 AN: 151970 Hom.: 2807 Cov.: 32

Gnomad AFR AF: 0.0903

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0707

Gnomad SAS AF: 0.0779

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.179 AC: 27195 AN: 152088 Hom.: 2807 Cov.: 32 AF XY: 0.175 AC XY: 12994 AN XY: 74348

African (AFR) AF: 0.0904 AC: 3751 AN: 41500

American (AMR) AF: 0.151 AC: 2308 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 736 AN: 3466

East Asian (EAS) AF: 0.0704 AC: 365 AN: 5182

South Asian (SAS) AF: 0.0788 AC: 380 AN: 4822

European-Finnish (FIN) AF: 0.260 AC: 2743 AN: 10534

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.239 AC: 16219 AN: 67990

Other (OTH) AF: 0.173 AC: 366 AN: 2112

Alfa AF: 0.214 Hom.: 470

Bravo AF: 0.167

Asia WGS AF: 0.0880 AC: 305 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.3
DANN	Benign	0.33
PhyloP100		0.66
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: rs10491167; hg19: chr17-61426698;