6-73353931-C-T

Variant names:

• chr6-73353931-C-T
• rs1582614694
• NM_001025290.3:c.214G>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001025290.3(DPPA5):​c.214G>A​(p.Gly72Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DPPA5 NM_001025290.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.98

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.834

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPPA5	NM_001025290.3	c.214G>A	p.Gly72Ser	missense_variant	Exon 2 of 3	ENST00000370370.4	NP_001020461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPPA5	ENST00000370370.4	c.214G>A	p.Gly72Ser	missense_variant	Exon 2 of 3	1	NM_001025290.3	ENSP00000359396.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Aganglionic megacolon Uncertain:1

May 16, 2019

Clinical Genetics, Erasmus University Medical Center

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.56	T
M_CAP	Uncertain	0.097	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.021	D
Sift4G	Benign	0.14	T
Polyphen		0.97	D
Vest4		0.81
MutPred		0.62		Gain of MoRF binding (P = 0.135);
MVP		0.63
MPC		1.6
ClinPred		0.99	D
GERP RS		3.7
Varity_R		0.33
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1582614694; hg19: chr6-74063654;