10-473224-G-C

Variant names:

• chr10-473224-G-C
• rs4881333
• NM_014974.3:c.158-675C>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.158-675C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,144 control chromosomes in the GnomAD database, including 16,143 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 0.43 (16143 hom., cov: 33)
• Consequence: DIP2C NM_014974.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIP2C	NM_014974.3	MANE Select	c.158-675C>G		intron	N/A	NP_055789.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIP2C	ENST00000280886.12	TSL:1 MANE Select	c.158-675C>G		intron	N/A	ENSP00000280886.6
	DIP2C	ENST00000634311.1	TSL:5	c.326-675C>G		intron	N/A	ENSP00000489203.1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65551 AN: 152026 Hom.: 16146 Cov.: 33

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.431 AC: 65538 AN: 152144 Hom.: 16143 Cov.: 33 AF XY: 0.442 AC XY: 32851 AN XY: 74366

African (AFR) AF: 0.173 AC: 7195 AN: 41524

American (AMR) AF: 0.516 AC: 7878 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 2016 AN: 3470

East Asian (EAS) AF: 0.645 AC: 3338 AN: 5174

South Asian (SAS) AF: 0.634 AC: 3057 AN: 4824

European-Finnish (FIN) AF: 0.592 AC: 6262 AN: 10570

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34309 AN: 67990

Other (OTH) AF: 0.447 AC: 946 AN: 2114

Alfa AF: 0.348 Hom.: 1038

Bravo AF: 0.416

Asia WGS AF: 0.583 AC: 2024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.015
DANN	Benign	0.26
PhyloP100		-1.8
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: rs4881333; hg19: chr10-519164;