chr10-520439-C-T

Variant names:

• chr10-520439-C-T
• rs11252926
• NM_014974.3:c.86-33909G>A

Variant summary

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

The NM_014974.3(DIP2C):​c.86-33909G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,166 control chromosomes in the GnomAD database, including 5,877 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 (5877 hom., cov: 34)
• Consequence: DIP2C NM_014974.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380
• Publications: 11 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 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.86-33909G>A		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.86-33909G>A		intron	N/A	ENSP00000280886.6	Q9Y2E4-1
	DIP2C	ENST00000634311.1	TSL:5	c.86-33909G>A		intron	N/A	ENSP00000489203.1	A0A0U1RQW6
	DIP2C	ENST00000931129.1		c.86-33909G>A		intron	N/A	ENSP00000601188.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37814 AN: 152048 Hom.: 5872 Cov.: 34

Gnomad AFR AF: 0.0700

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.0688

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.249 AC: 37827 AN: 152166 Hom.: 5877 Cov.: 34 AF XY: 0.247 AC XY: 18359 AN XY: 74394

African (AFR) AF: 0.0698 AC: 2898 AN: 41524

American (AMR) AF: 0.297 AC: 4540 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 936 AN: 3470

East Asian (EAS) AF: 0.0692 AC: 359 AN: 5188

South Asian (SAS) AF: 0.242 AC: 1165 AN: 4822

European-Finnish (FIN) AF: 0.313 AC: 3308 AN: 10584

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23586 AN: 67972

Other (OTH) AF: 0.277 AC: 584 AN: 2112

Alfa AF: 0.293 Hom.: 13668

Bravo AF: 0.237

Asia WGS AF: 0.182 AC: 634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.30
PhyloP100		0.038
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: rs11252926; hg19: chr10-566379;