rs2460111

Variant names:

• chr17-63237911-G-A
• rs2460111
• NM_001394998.1:c.867G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-63237911-G-A
• chr17-63237911-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001394998.1(TANC2):​c.867G>A​(p.Gln289Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 1,577,594 control chromosomes in the GnomAD database, including 216,744 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.60 (29661 hom., cov: 31)
  • Exomes 𝑓: 0.51 (187083 hom.)
• Consequence: TANC2 NM_001394998.1 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.40
• Publications: 23 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 17-63237911-G-A is Benign according to our data. Variant chr17-63237911-G-A is described in ClinVar as Benign. ClinVar VariationId is 3059740.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.4 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.857 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.867G>A	p.Gln289Gln	synonymous	Exon 8 of 28	NP_001381927.1
	TANC2	NM_001411076.1		c.645G>A	p.Gln215Gln	synonymous	Exon 7 of 27	NP_001398005.1
	TANC2	NM_025185.4		c.645G>A	p.Gln215Gln	synonymous	Exon 7 of 26	NP_079461.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANC2	ENST00000689528.1	MANE Select	c.867G>A	p.Gln289Gln	synonymous	Exon 8 of 28	ENSP00000510600.1
	TANC2	ENST00000424789.6	TSL:1	c.645G>A	p.Gln215Gln	synonymous	Exon 6 of 25	ENSP00000387593.2
	TANC2	ENST00000583356.5	TSL:1	c.429G>A	p.Gln143Gln	synonymous	Exon 3 of 21	ENSP00000462109.1

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90738 AN: 151784 Hom.: 29601 Cov.: 31

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.535

GnomAD2 exomes AF: 0.488 AC: 95380 AN: 195288 AF XY: 0.487

Gnomad AFR exome AF: 0.875

Gnomad AMR exome AF: 0.405

Gnomad ASJ exome AF: 0.477

Gnomad EAS exome AF: 0.151

Gnomad FIN exome AF: 0.572

Gnomad NFE exome AF: 0.508

Gnomad OTH exome AF: 0.481

GnomAD4 exome AF: 0.505 AC: 720526 AN: 1425692 Hom.: 187083 Cov.: 47 AF XY: 0.504 AC XY: 355404 AN XY: 705436

African (AFR) AF: 0.880 AC: 28879 AN: 32826

American (AMR) AF: 0.417 AC: 16457 AN: 39470

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 12231 AN: 25396

East Asian (EAS) AF: 0.220 AC: 8447 AN: 38348

South Asian (SAS) AF: 0.489 AC: 39579 AN: 80972

European-Finnish (FIN) AF: 0.563 AC: 28841 AN: 51188

Middle Eastern (MID) AF: 0.482 AC: 2758 AN: 5722

European-Non Finnish (NFE) AF: 0.506 AC: 553277 AN: 1092686

Other (OTH) AF: 0.509 AC: 30057 AN: 59084

GnomAD4 genome AF: 0.598 AC: 90855 AN: 151902 Hom.: 29661 Cov.: 31 AF XY: 0.593 AC XY: 43989 AN XY: 74210

African (AFR) AF: 0.864 AC: 35848 AN: 41480

American (AMR) AF: 0.477 AC: 7273 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1658 AN: 3466

East Asian (EAS) AF: 0.174 AC: 897 AN: 5164

South Asian (SAS) AF: 0.489 AC: 2357 AN: 4818

European-Finnish (FIN) AF: 0.570 AC: 5996 AN: 10514

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35003 AN: 67892

Other (OTH) AF: 0.539 AC: 1138 AN: 2112

Alfa AF: 0.530 Hom.: 43958

Bravo AF: 0.599

Asia WGS AF: 0.409 AC: 1426 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TANC2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	3.6
DANN	Benign	0.75
PhyloP100		1.4
Mutation Taster		=99/1	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: rs2460111; hg19: chr17-61315272; COSMIC: COSV67331922;