chr10-362368-A-T

Variant names:

• chr10-362368-A-T
• rs10904051
• NM_014974.3:c.2794+122T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014974.3(DIP2C):​c.2794+122T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000199 in 1,004,622 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000020 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

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>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.2794+122T>A		intron	N/A	ENSP00000280886.6
	DIP2C	ENST00000634311.1	TSL:5	c.2962+122T>A		intron	N/A	ENSP00000489203.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000199 AC: 2 AN: 1004622 Hom.: 0 AF XY: 0.00000202 AC XY: 1 AN XY: 495216

African (AFR) AF: 0.00 AC: 0 AN: 23016

American (AMR) AF: 0.00 AC: 0 AN: 20078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16878

East Asian (EAS) AF: 0.00 AC: 0 AN: 34006

South Asian (SAS) AF: 0.00 AC: 0 AN: 50272

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2978

European-Non Finnish (NFE) AF: 0.00000259 AC: 2 AN: 772756

Other (OTH) AF: 0.00 AC: 0 AN: 44012

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.8
DANN	Benign	0.91
PhyloP100		0.73

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;