6-73353369-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001025290.3(DPPA5):​c.302A>G​(p.Lys101Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000452 in 1,614,100 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K101Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00047 ( 1 hom. )

Consequence

DPPA5
NM_001025290.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.921
Variant links:
Genes affected
DPPA5 (HGNC:19201): (developmental pluripotency associated 5) This gene encodes a protein that may function in the control of cell pluripotency and early embryogenesis. Expression of this gene is a specific marker for pluripotent stem cells. Pseudogenes of this gene are located on the short arm of chromosome 10 and the long arm of chromosomes 14 and 19. [provided by RefSeq, Dec 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.038155705).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DPPA5NM_001025290.3 linkc.302A>G p.Lys101Arg missense_variant Exon 3 of 3 ENST00000370370.4 NP_001020461.1 A6NC42

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DPPA5ENST00000370370.4 linkc.302A>G p.Lys101Arg missense_variant Exon 3 of 3 1 NM_001025290.3 ENSP00000359396.3 A6NC42

Frequencies

GnomAD3 genomes
AF:
0.000243
AC:
37
AN:
152098
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000410
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000265
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000187
AC:
47
AN:
251494
Hom.:
0
AF XY:
0.000154
AC XY:
21
AN XY:
135922
show subpopulations
Gnomad AFR exome
AF:
0.000615
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000281
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000473
AC:
692
AN:
1461884
Hom.:
1
Cov.:
31
AF XY:
0.000441
AC XY:
321
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000593
Gnomad4 OTH exome
AF:
0.000281
GnomAD4 genome
AF:
0.000243
AC:
37
AN:
152216
Hom.:
0
Cov.:
32
AF XY:
0.000228
AC XY:
17
AN XY:
74424
show subpopulations
Gnomad4 AFR
AF:
0.000409
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000265
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000364
Hom.:
0
Bravo
AF:
0.000257
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000189
AC:
23
EpiCase
AF:
0.000218
EpiControl
AF:
0.000296

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 27, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.302A>G (p.K101R) alteration is located in exon 3 (coding exon 3) of the DPPA5 gene. This alteration results from a A to G substitution at nucleotide position 302, causing the lysine (K) at amino acid position 101 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.071
BayesDel_addAF
Benign
-0.66
T
BayesDel_noAF
Benign
-0.80
CADD
Benign
6.1
DANN
Benign
0.88
DEOGEN2
Benign
0.12
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.56
T
M_CAP
Benign
0.0030
T
MetaRNN
Benign
0.038
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.41
N
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-0.98
N
REVEL
Benign
0.091
Sift
Benign
0.24
T
Sift4G
Benign
0.20
T
Polyphen
0.0
B
Vest4
0.043
MVP
0.13
MPC
0.62
ClinPred
0.0090
T
GERP RS
-5.6
Varity_R
0.086
gMVP
0.62

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: rs12200929; hg19: chr6-74063092; API