chr21-46497082-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_015151.4(DIP2A):​c.378G>A​(p.Ser126Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000495 in 1,613,784 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00051 ( 1 hom. )

Consequence

DIP2A
NM_015151.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -2.06
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 21-46497082-G-A is Benign according to our data. Variant chr21-46497082-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652831.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-2.06 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DIP2ANM_015151.4 linkuse as main transcriptc.378G>A p.Ser126Ser synonymous_variant 4/38 ENST00000417564.3 NP_055966.2 Q14689-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DIP2AENST00000417564.3 linkuse as main transcriptc.378G>A p.Ser126Ser synonymous_variant 4/381 NM_015151.4 ENSP00000392066.2 Q14689-1

Frequencies

GnomAD3 genomes
AF:
0.000375
AC:
57
AN:
152166
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00404
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000485
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000474
AC:
118
AN:
248868
Hom.:
0
AF XY:
0.000533
AC XY:
72
AN XY:
135014
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000581
Gnomad ASJ exome
AF:
0.00378
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000950
Gnomad FIN exome
AF:
0.0000464
Gnomad NFE exome
AF:
0.000408
Gnomad OTH exome
AF:
0.000331
GnomAD4 exome
AF:
0.000508
AC:
742
AN:
1461500
Hom.:
1
Cov.:
30
AF XY:
0.000535
AC XY:
389
AN XY:
727032
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000448
Gnomad4 ASJ exome
AF:
0.00360
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000951
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000470
Gnomad4 OTH exome
AF:
0.000596
GnomAD4 genome
AF:
0.000374
AC:
57
AN:
152284
Hom.:
0
Cov.:
33
AF XY:
0.000390
AC XY:
29
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00404
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000485
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000731
Hom.:
0
Bravo
AF:
0.000302
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.000356

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

DIP2A-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesMay 24, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJan 01, 2023DIP2A: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.11
DANN
Benign
0.60
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs181610004; hg19: chr21-47916995; COSMIC: COSV59472292; API