rs7279002

Variant names:

• chr21-46490610-A-G
• rs7279002
• NM_015151.4:c.174A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_015151.4(DIP2A):​c.174A>G​(p.Pro58Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,566,230 control chromosomes in the GnomAD database, including 54,994 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.31 (8238 hom., cov: 33)
  • Exomes 𝑓: 0.25 (46756 hom.)
• Consequence: DIP2A NM_015151.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.898

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 21-46490610-A-G is Benign according to our data. Variant chr21-46490610-A-G is described in ClinVar as [Benign]. Clinvar id is 3060043.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.898 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIP2A	NM_015151.4	c.174A>G	p.Pro58Pro	synonymous_variant	Exon 3 of 38	ENST00000417564.3	NP_055966.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIP2A	ENST00000417564.3	c.174A>G	p.Pro58Pro	synonymous_variant	Exon 3 of 38	1	NM_015151.4	ENSP00000392066.2

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47745 AN: 152000 Hom.: 8231 Cov.: 33

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.324

GnomAD3 exomes AF: 0.273 AC: 48934 AN: 179014 Hom.: 7196 AF XY: 0.276 AC XY: 26260 AN XY: 95234

Gnomad AFR exome AF: 0.463

Gnomad AMR exome AF: 0.199

Gnomad ASJ exome AF: 0.258

Gnomad EAS exome AF: 0.425

Gnomad SAS exome AF: 0.309

Gnomad FIN exome AF: 0.274

Gnomad NFE exome AF: 0.239

Gnomad OTH exome AF: 0.268

GnomAD4 exome AF: 0.250 AC: 354083 AN: 1414112 Hom.: 46756 Cov.: 32 AF XY: 0.252 AC XY: 176410 AN XY: 699130

Gnomad4 AFR exome AF: 0.481

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.257

Gnomad4 EAS exome AF: 0.438

Gnomad4 SAS exome AF: 0.309

Gnomad4 FIN exome AF: 0.273

Gnomad4 NFE exome AF: 0.231

Gnomad4 OTH exome AF: 0.276

GnomAD4 genome AF: 0.314 AC: 47781 AN: 152118 Hom.: 8238 Cov.: 33 AF XY: 0.313 AC XY: 23261 AN XY: 74380

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.328

Alfa AF: 0.259 Hom.: 7143

Bravo AF: 0.318

Asia WGS AF: 0.387 AC: 1347 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

DIP2A-related disorder Benign:1

May 15, 2020

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	-0.93
CADD	Benign	3.3
DANN	Benign	0.41

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: rs7279002; hg19: chr21-47910523; COSMIC: COSV59472211;