rs17293454

Variant names:

• chr10-587555-T-C
• rs17293454
• NM_014974.3:c.86-101025A>G

Variant summary

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

The NM_014974.3(DIP2C):​c.86-101025A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0771 in 152,162 control chromosomes in the GnomAD database, including 652 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 0.077 (652 hom., cov: 32)
• Consequence: DIP2C NM_014974.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94
• Publications: 3 publications found

Genes affected

DIP2C (HGNC:29150): (disco interacting protein 2 homolog C) This gene encodes a member of the disco-interacting protein homolog 2 family. The protein shares strong similarity with a Drosophila protein which interacts with the transcription factor disco and is expressed in the nervous system. [provided by RefSeq, Oct 2008]

DIP2C Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014974.3. 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
	DIP2C	NM_014974.3	MANE Select	c.86-101025A>G		intron	N/A	NP_055789.1	Q9Y2E4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIP2C	ENST00000280886.12	TSL:1 MANE Select	c.86-101025A>G		intron	N/A	ENSP00000280886.6	Q9Y2E4-1
	DIP2C	ENST00000634311.1	TSL:5	c.86-101025A>G		intron	N/A	ENSP00000489203.1	A0A0U1RQW6
	DIP2C	ENST00000931129.1		c.86-101025A>G		intron	N/A	ENSP00000601188.1

Frequencies

GnomAD3 genomes AF: 0.0771 AC: 11727 AN: 152042 Hom.: 652 Cov.: 32

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.0417

Gnomad ASJ AF: 0.0873

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0564

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.0718

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

GnomAD4 genome AF: 0.0771 AC: 11726 AN: 152162 Hom.: 652 Cov.: 32 AF XY: 0.0771 AC XY: 5734 AN XY: 74376

African (AFR) AF: 0.0196 AC: 814 AN: 41526

American (AMR) AF: 0.0417 AC: 638 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0873 AC: 303 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0566 AC: 273 AN: 4822

European-Finnish (FIN) AF: 0.139 AC: 1468 AN: 10574

Middle Eastern (MID) AF: 0.0548 AC: 16 AN: 292

European-Non Finnish (NFE) AF: 0.118 AC: 7998 AN: 67974

Other (OTH) AF: 0.0706 AC: 149 AN: 2110

Alfa AF: 0.108 Hom.: 616

Bravo AF: 0.0672

Asia WGS AF: 0.0240 AC: 83 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.1
DANN	Benign	0.50
PhyloP100		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs17293454; hg19: chr10-633495;