rs17221323

Variant names:

• chr10-572745-T-C
• rs17221323
• NM_014974.3:c.86-86215A>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.86-86215A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,016 control chromosomes in the GnomAD database, including 1,630 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 0.13 (1630 hom., cov: 32)
• Consequence: DIP2C NM_014974.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIP2C	NM_014974.3	c.86-86215A>G		intron_variant	Intron 1 of 36	ENST00000280886.12	NP_055789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIP2C	ENST00000280886.12	c.86-86215A>G		intron_variant	Intron 1 of 36	1	NM_014974.3	ENSP00000280886.6
DIP2C	ENST00000634311.1	c.86-86215A>G		intron_variant	Intron 1 of 38	5		ENSP00000489203.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19314 AN: 151898 Hom.: 1629 Cov.: 32

Gnomad AFR AF: 0.0328

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.127 AC: 19307 AN: 152016 Hom.: 1630 Cov.: 32 AF XY: 0.125 AC XY: 9302 AN XY: 74312

African (AFR) AF: 0.0326 AC: 1354 AN: 41476

American (AMR) AF: 0.100 AC: 1534 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 800 AN: 3466

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5180

South Asian (SAS) AF: 0.117 AC: 560 AN: 4798

European-Finnish (FIN) AF: 0.146 AC: 1542 AN: 10540

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13022 AN: 67968

Other (OTH) AF: 0.140 AC: 296 AN: 2112

Alfa AF: 0.175 Hom.: 2352

Bravo AF: 0.119

Asia WGS AF: 0.0530 AC: 185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.42
PhyloP100		-0.093
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: rs17221323; hg19: chr10-618685;