chr10-528952-C-G

Variant names:

• chr10-528952-C-G
• rs7912017
• NM_014974.3:c.86-42422G>C

Variant summary

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

The NM_014974.3(DIP2C):​c.86-42422G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,162 control chromosomes in the GnomAD database, including 6,389 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 0.25 (6389 hom., cov: 32)
• Consequence: DIP2C NM_014974.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.494
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIP2C	NM_014974.3	c.86-42422G>C		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.86-42422G>C		intron_variant	Intron 1 of 36	1	NM_014974.3	ENSP00000280886.6
DIP2C	ENST00000634311.1	c.86-42422G>C		intron_variant	Intron 1 of 38	5		ENSP00000489203.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37656 AN: 152044 Hom.: 6364 Cov.: 32

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.248 AC: 37717 AN: 152162 Hom.: 6389 Cov.: 32 AF XY: 0.242 AC XY: 18025 AN XY: 74392

African (AFR) AF: 0.482 AC: 19988 AN: 41482

American (AMR) AF: 0.169 AC: 2587 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 539 AN: 3466

East Asian (EAS) AF: 0.269 AC: 1391 AN: 5162

South Asian (SAS) AF: 0.142 AC: 682 AN: 4816

European-Finnish (FIN) AF: 0.129 AC: 1370 AN: 10610

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10479 AN: 68008

Other (OTH) AF: 0.222 AC: 470 AN: 2116

Alfa AF: 0.214 Hom.: 602

Bravo AF: 0.259

Asia WGS AF: 0.200 AC: 696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.88
DANN	Benign	0.36
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7912017; hg19: chr10-574892;