10-388696-C-T

Variant names:

• chr10-388696-C-T
• rs7914284
• NM_014974.3:c.1598-887G>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.1598-887G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 152,082 control chromosomes in the GnomAD database, including 22,049 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 0.54 (22049 hom., cov: 33)
• Consequence: DIP2C NM_014974.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.81
• Publications: 0 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 = 0.707 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.1598-887G>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.1598-887G>A		intron	N/A	ENSP00000280886.6	Q9Y2E4-1
	DIP2C	ENST00000634311.1	TSL:5	c.1766-887G>A		intron	N/A	ENSP00000489203.1	A0A0U1RQW6
	DIP2C	ENST00000931129.1		c.1766-887G>A		intron	N/A	ENSP00000601188.1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81451 AN: 151964 Hom.: 22045 Cov.: 33

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.536 AC: 81481 AN: 152082 Hom.: 22049 Cov.: 33 AF XY: 0.545 AC XY: 40490 AN XY: 74334

African (AFR) AF: 0.455 AC: 18868 AN: 41448

American (AMR) AF: 0.575 AC: 8788 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2057 AN: 3472

East Asian (EAS) AF: 0.726 AC: 3749 AN: 5162

South Asian (SAS) AF: 0.684 AC: 3293 AN: 4812

European-Finnish (FIN) AF: 0.609 AC: 6447 AN: 10592

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.538 AC: 36604 AN: 67992

Other (OTH) AF: 0.525 AC: 1107 AN: 2110

Alfa AF: 0.535 Hom.: 4315

Bravo AF: 0.530

Asia WGS AF: 0.678 AC: 2357 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	0.043
DANN	Benign	0.59
PhyloP100		-3.8
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: rs7914284; hg19: chr10-434636;