10-277343-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014974.3(DIP2C):c.4653T>C(p.Tyr1551=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,613,930 control chromosomes in the GnomAD database, including 58,175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5667 hom., cov: 32)
  • Exomes 𝑓: 0.27 (52508 hom.)
• Consequence: DIP2C NM_014974.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.124

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 10-277343-A-G is Benign according to our data. Variant chr10-277343-A-G is described in ClinVar as [Benign]. Clinvar id is 1598742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.124 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIP2C	NM_014974.3	c.4653T>C	p.Tyr1551=	synonymous_variant	37/37	ENST00000280886.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIP2C	ENST00000280886.12	c.4653T>C	p.Tyr1551=	synonymous_variant	37/37	1	NM_014974.3	P1
DIP2C	ENST00000634311.1	c.4851T>C	p.Tyr1617=	synonymous_variant	39/39	5

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41183 AN: 152026 Hom.: 5657 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.281

GnomAD3 exomes AF: 0.265 AC: 66612 AN: 251334 Hom.: 9246 AF XY: 0.273 AC XY: 37127 AN XY: 135856

Gnomad AFR exome AF: 0.297

Gnomad AMR exome AF: 0.180

Gnomad ASJ exome AF: 0.230

Gnomad EAS exome AF: 0.246

Gnomad SAS exome AF: 0.355

Gnomad FIN exome AF: 0.272

Gnomad NFE exome AF: 0.266

Gnomad OTH exome AF: 0.275

GnomAD4 exome AF: 0.265 AC: 388057 AN: 1461786 Hom.: 52508 Cov.: 34 AF XY: 0.269 AC XY: 195913 AN XY: 727196

Gnomad4 AFR exome AF: 0.298

Gnomad4 AMR exome AF: 0.188

Gnomad4 ASJ exome AF: 0.230

Gnomad4 EAS exome AF: 0.228

Gnomad4 SAS exome AF: 0.354

Gnomad4 FIN exome AF: 0.267

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.271 AC: 41199 AN: 152144 Hom.: 5667 Cov.: 32 AF XY: 0.272 AC XY: 20255 AN XY: 74390

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.278

Alfa AF: 0.266 Hom.: 12158

Bravo AF: 0.264

Asia WGS AF: 0.296 AC: 1027 AN: 3478

EpiCase AF: 0.273

EpiControl AF: 0.269

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

DIP2C-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	1.8
Dann	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs3740304; hg19: chr10-323283; COSMIC: COSV55173938; COSMIC: COSV55173938;