rs2070435

Variant names:

• chr21-46541798-G-A
• rs2070435
• NM_015151.4:c.2079G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_015151.4(DIP2A):​c.2079G>A​(p.Leu693Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 1,613,500 control chromosomes in the GnomAD database, including 90,971 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.37 (10961 hom., cov: 32)
  • Exomes 𝑓: 0.33 (80010 hom.)
• Consequence: DIP2A NM_015151.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0400

Genes affected

DIP2A (HGNC:17217): (disco interacting protein 2 homolog A) The protein encoded by this gene may be involved in axon patterning in the central nervous system. This gene is not highly expressed. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 21-46541798-G-A is Benign according to our data. Variant chr21-46541798-G-A is described in ClinVar as [Benign]. Clinvar id is 3060508.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.04 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIP2A	NM_015151.4	c.2079G>A	p.Leu693Leu	synonymous_variant	Exon 18 of 38	ENST00000417564.3	NP_055966.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIP2A	ENST00000417564.3	c.2079G>A	p.Leu693Leu	synonymous_variant	Exon 18 of 38	1	NM_015151.4	ENSP00000392066.2

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56034 AN: 151868 Hom.: 10931 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.376

GnomAD2 exomes AF: 0.328 AC: 81753 AN: 249152 AF XY: 0.329

Gnomad AFR exome AF: 0.503

Gnomad AMR exome AF: 0.231

Gnomad ASJ exome AF: 0.297

Gnomad EAS exome AF: 0.428

Gnomad FIN exome AF: 0.305

Gnomad NFE exome AF: 0.328

Gnomad OTH exome AF: 0.326

GnomAD4 exome AF: 0.328 AC: 478794 AN: 1461514 Hom.: 80010 Cov.: 40 AF XY: 0.327 AC XY: 238017 AN XY: 727034

Gnomad4 AFR exome AF: 0.507 AC: 16956 AN: 33474

Gnomad4 AMR exome AF: 0.233 AC: 10402 AN: 44716

Gnomad4 ASJ exome AF: 0.295 AC: 7707 AN: 26130

Gnomad4 EAS exome AF: 0.438 AC: 17374 AN: 39696

Gnomad4 SAS exome AF: 0.320 AC: 27570 AN: 86252

Gnomad4 FIN exome AF: 0.308 AC: 16456 AN: 53388

Gnomad4 NFE exome AF: 0.323 AC: 359550 AN: 1111720

Gnomad4 Remaining exome AF: 0.341 AC: 20571 AN: 60370

GnomAD4 genome AF: 0.369 AC: 56116 AN: 151986 Hom.: 10961 Cov.: 32 AF XY: 0.364 AC XY: 26997 AN XY: 74258

Gnomad4 AFR AF: 0.498 AC: 0.497611 AN: 0.497611

Gnomad4 AMR AF: 0.273 AC: 0.272703 AN: 0.272703

Gnomad4 ASJ AF: 0.303 AC: 0.303458 AN: 0.303458

Gnomad4 EAS AF: 0.425 AC: 0.425223 AN: 0.425223

Gnomad4 SAS AF: 0.330 AC: 0.329663 AN: 0.329663

Gnomad4 FIN AF: 0.300 AC: 0.300493 AN: 0.300493

Gnomad4 NFE AF: 0.324 AC: 0.324078 AN: 0.324078

Gnomad4 OTH AF: 0.379 AC: 0.379147 AN: 0.379147

Alfa AF: 0.334 Hom.: 8315

Bravo AF: 0.375

Asia WGS AF: 0.407 AC: 1417 AN: 3478

EpiCase AF: 0.319

EpiControl AF: 0.329

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

DIP2A-related disorder Benign:1

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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	-0.78
CADD	Benign	0.95
DANN	Benign	0.48
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

Publications

LitVar

Other links and lift over

dbSNP: rs2070435; hg19: chr21-47961711; COSMIC: COSV59472230;