chr17-63076018-C-G

Variant names:

• chr17-63076018-C-G
• rs10512498
• NM_001394998.1:c.139+2004C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001394998.1(TANC2):​c.139+2004C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 152,114 control chromosomes in the GnomAD database, including 98 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 0.034 (98 hom., cov: 32)
• Consequence: TANC2 NM_001394998.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 2 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=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0336 (5108/152114) while in subpopulation NFE AF = 0.0442 (3003/67972). AF 95% confidence interval is 0.0429. There are 98 homozygotes in GnomAd4. There are 2425 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 5108 AD gene.

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.139+2004C>G		intron	N/A	NP_001381927.1	A0A8I5KXR5
	TANC2	NM_001411076.1		c.139+2004C>G		intron	N/A	NP_001398005.1	Q9HCD6-2
	TANC2	NM_025185.4		c.139+2004C>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.139+2004C>G		intron	N/A	ENSP00000510600.1	A0A8I5KXR5
	TANC2	ENST00000424789.6	TSL:1	c.139+2004C>G		intron	N/A	ENSP00000387593.2	Q9HCD6-1
	TANC2	ENST00000389520.8	TSL:5	c.139+2004C>G		intron	N/A	ENSP00000374171.4	Q9HCD6-2

Frequencies

GnomAD3 genomes AF: 0.0336 AC: 5108 AN: 151996 Hom.: 97 Cov.: 32

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0405

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.0208

Gnomad FIN AF: 0.0313

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0442

Gnomad OTH AF: 0.0411

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

GnomAD4 genome AF: 0.0336 AC: 5108 AN: 152114 Hom.: 98 Cov.: 32 AF XY: 0.0326 AC XY: 2425 AN XY: 74356

African (AFR) AF: 0.0159 AC: 658 AN: 41496

American (AMR) AF: 0.0405 AC: 618 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0513 AC: 178 AN: 3472

East Asian (EAS) AF: 0.0112 AC: 58 AN: 5186

South Asian (SAS) AF: 0.0210 AC: 101 AN: 4812

European-Finnish (FIN) AF: 0.0313 AC: 331 AN: 10582

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0442 AC: 3003 AN: 67972

Other (OTH) AF: 0.0417 AC: 88 AN: 2112

Alfa AF: 0.0344 Hom.: 10

Bravo AF: 0.0335

Asia WGS AF: 0.0350 AC: 121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.66
PhyloP100		-0.031
Mutation Taster		=100/0	polymorphism

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: rs10512498; hg19: chr17-61153379;