17-63316296-A-AAAGCTC

Variant names:

• chr17-63316296-A-AAAGCTC
• rs16715
• NM_001394998.1:c.1441+1634_1441+1639dupAAGCTC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001394998.1(TANC2):​c.1441+1634_1441+1639dupAAGCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (18168 hom., cov: 0)
• Consequence: TANC2 NM_001394998.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.701
• 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: Illumina, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000233635 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANC2	NM_001394998.1	MANE Select	c.1441+1634_1441+1639dupAAGCTC		intron	N/A	NP_001381927.1
	TANC2	NM_001411076.1		c.1219+1634_1219+1639dupAAGCTC		intron	N/A	NP_001398005.1
	TANC2	NM_025185.4		c.1219+1634_1219+1639dupAAGCTC		intron	N/A	NP_079461.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANC2	ENST00000689528.1	MANE Select	c.1441+1627_1441+1628insAAGCTC		intron	N/A	ENSP00000510600.1
	TANC2	ENST00000424789.6	TSL:1	c.1219+1627_1219+1628insAAGCTC		intron	N/A	ENSP00000387593.2
	TANC2	ENST00000583356.5	TSL:1	c.1003+1627_1003+1628insAAGCTC		intron	N/A	ENSP00000462109.1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66567 AN: 151292 Hom.: 18119 Cov.: 0

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.0943

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.379

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

GnomAD4 genome AF: 0.440 AC: 66673 AN: 151410 Hom.: 18168 Cov.: 0 AF XY: 0.438 AC XY: 32404 AN XY: 73992

African (AFR) AF: 0.779 AC: 32025 AN: 41100

American (AMR) AF: 0.338 AC: 5154 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1035 AN: 3464

East Asian (EAS) AF: 0.0945 AC: 490 AN: 5186

South Asian (SAS) AF: 0.415 AC: 1990 AN: 4798

European-Finnish (FIN) AF: 0.344 AC: 3612 AN: 10496

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21220 AN: 67824

Other (OTH) AF: 0.384 AC: 808 AN: 2102

Alfa AF: 0.221 Hom.: 440

Asia WGS AF: 0.326 AC: 1137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs16715; hg19: chr17-61393657;