chr10-362368-A-G

Variant names:

• chr10-362368-A-G
• rs10904051
• NM_014974.3:c.2794+122T>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.2794+122T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 1,154,162 control chromosomes in the GnomAD database, including 142,570 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 0.40 (13939 hom., cov: 32)
  • Exomes 𝑓: 0.50 (128631 hom.)
• Consequence: DIP2C NM_014974.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.726
• 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=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.531 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.2794+122T>C		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.2794+122T>C		intron	N/A	ENSP00000280886.6
	DIP2C	ENST00000634311.1	TSL:5	c.2962+122T>C		intron	N/A	ENSP00000489203.1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60422 AN: 151914 Hom.: 13934 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.427

GnomAD4 exome AF: 0.497 AC: 498333 AN: 1002130 Hom.: 128631 AF XY: 0.494 AC XY: 244229 AN XY: 494004

African (AFR) AF: 0.130 AC: 3000 AN: 22994

American (AMR) AF: 0.404 AC: 8092 AN: 20048

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 7949 AN: 16840

East Asian (EAS) AF: 0.258 AC: 8776 AN: 33980

South Asian (SAS) AF: 0.374 AC: 18743 AN: 50162

European-Finnish (FIN) AF: 0.453 AC: 18371 AN: 40558

Middle Eastern (MID) AF: 0.481 AC: 1426 AN: 2962

European-Non Finnish (NFE) AF: 0.534 AC: 411448 AN: 770696

Other (OTH) AF: 0.468 AC: 20528 AN: 43890

GnomAD4 genome AF: 0.398 AC: 60437 AN: 152032 Hom.: 13939 Cov.: 32 AF XY: 0.392 AC XY: 29121 AN XY: 74292

African (AFR) AF: 0.152 AC: 6317 AN: 41498

American (AMR) AF: 0.429 AC: 6553 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1651 AN: 3470

East Asian (EAS) AF: 0.288 AC: 1484 AN: 5152

South Asian (SAS) AF: 0.364 AC: 1751 AN: 4810

European-Finnish (FIN) AF: 0.442 AC: 4670 AN: 10558

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.535 AC: 36393 AN: 67970

Other (OTH) AF: 0.426 AC: 899 AN: 2108

Alfa AF: 0.474 Hom.: 10043

Bravo AF: 0.383

Asia WGS AF: 0.337 AC: 1175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.3
DANN	Benign	0.86
PhyloP100		0.73
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: rs10904051; hg19: chr10-408308;