17-63210084-T-G

Variant names:

• chr17-63210084-T-G
• rs1518774
• NM_001394998.1:c.769+9127T>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.769+9127T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 152,004 control chromosomes in the GnomAD database, including 27,987 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 0.58 (27987 hom., cov: 31)
• Consequence: TANC2 NM_001394998.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.809 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.769+9127T>G		intron	N/A	NP_001381927.1
	TANC2	NM_001411076.1		c.547+9127T>G		intron	N/A	NP_001398005.1
	TANC2	NM_025185.4		c.547+9127T>G		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.769+9127T>G		intron	N/A	ENSP00000510600.1
	TANC2	ENST00000424789.6	TSL:1	c.547+9127T>G		intron	N/A	ENSP00000387593.2
	TANC2	ENST00000583356.5	TSL:1	c.331+9127T>G		intron	N/A	ENSP00000462109.1

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88780 AN: 151886 Hom.: 27943 Cov.: 31

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.585 AC: 88884 AN: 152004 Hom.: 27987 Cov.: 31 AF XY: 0.580 AC XY: 43079 AN XY: 74290

African (AFR) AF: 0.816 AC: 33840 AN: 41476

American (AMR) AF: 0.473 AC: 7218 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1662 AN: 3472

East Asian (EAS) AF: 0.174 AC: 897 AN: 5170

South Asian (SAS) AF: 0.493 AC: 2373 AN: 4814

European-Finnish (FIN) AF: 0.569 AC: 5989 AN: 10530

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35110 AN: 67952

Other (OTH) AF: 0.527 AC: 1110 AN: 2108

Alfa AF: 0.507 Hom.: 9240

Bravo AF: 0.583

Asia WGS AF: 0.413 AC: 1440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.2
DANN	Benign	0.64
PhyloP100		0.60
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: rs1518774; hg19: chr17-61287445;