10-420890-A-G

Variant names:

• chr10-420890-A-G
• rs10795122
• NM_014974.3:c.605-1691T>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.605-1691T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,020 control chromosomes in the GnomAD database, including 11,018 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 0.35 (11018 hom., cov: 32)
• Consequence: DIP2C NM_014974.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.687
• Publications: 4 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 = 0.465 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.605-1691T>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.605-1691T>C		intron	N/A	ENSP00000280886.6
	DIP2C	ENST00000634311.1	TSL:5	c.773-1691T>C		intron	N/A	ENSP00000489203.1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53885 AN: 151902 Hom.: 11007 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.355 AC: 53908 AN: 152020 Hom.: 11018 Cov.: 32 AF XY: 0.351 AC XY: 26047 AN XY: 74290

African (AFR) AF: 0.141 AC: 5832 AN: 41492

American (AMR) AF: 0.380 AC: 5808 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1329 AN: 3468

East Asian (EAS) AF: 0.322 AC: 1661 AN: 5156

South Asian (SAS) AF: 0.332 AC: 1601 AN: 4818

European-Finnish (FIN) AF: 0.411 AC: 4341 AN: 10552

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31916 AN: 67940

Other (OTH) AF: 0.374 AC: 787 AN: 2106

Alfa AF: 0.387 Hom.: 1775

Bravo AF: 0.341

Asia WGS AF: 0.342 AC: 1188 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	0.46
DANN	Benign	0.38
PhyloP100		-0.69
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: rs10795122; hg19: chr10-466830;