10-555149-C-T

Variant names:

• chr10-555149-C-T
• rs816650
• NM_014974.3:c.86-68619G>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.86-68619G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 151,834 control chromosomes in the GnomAD database, including 3,527 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 0.16 (3527 hom., cov: 32)
• Consequence: DIP2C NM_014974.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.530
• Publications: 6 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 (AFR) allele frequency at 95% confidence interval = 0.38 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.86-68619G>A		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.86-68619G>A		intron	N/A	ENSP00000280886.6
	DIP2C	ENST00000634311.1	TSL:5	c.86-68619G>A		intron	N/A	ENSP00000489203.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 24982 AN: 151724 Hom.: 3516 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0864

Gnomad ASJ AF: 0.0753

Gnomad EAS AF: 0.0863

Gnomad SAS AF: 0.0812

Gnomad FIN AF: 0.0910

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0796

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.165 AC: 25027 AN: 151834 Hom.: 3527 Cov.: 32 AF XY: 0.161 AC XY: 11931 AN XY: 74178

African (AFR) AF: 0.385 AC: 15930 AN: 41328

American (AMR) AF: 0.0865 AC: 1322 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0753 AC: 261 AN: 3468

East Asian (EAS) AF: 0.0866 AC: 449 AN: 5182

South Asian (SAS) AF: 0.0807 AC: 387 AN: 4794

European-Finnish (FIN) AF: 0.0910 AC: 956 AN: 10506

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0796 AC: 5409 AN: 67954

Other (OTH) AF: 0.125 AC: 263 AN: 2110

Alfa AF: 0.108 Hom.: 4119

Bravo AF: 0.172

Asia WGS AF: 0.0970 AC: 338 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	2.6
DANN	Benign	0.17
PhyloP100		0.53
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs816650; hg19: chr10-601089;