Variant 12-63569344-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_173812.5(DPY19L2):c.2006G>A(p.Arg669Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000861 in 1,579,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000080 ( 0 hom. )

Consequence

DPY19L2
NM_173812.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.32

Variant links:

Genes affected

DPY19L2 (HGNC:19414): (dpy-19 like 2) The protein encoded by this gene belongs to the dpy-19 family. It is highly expressed in testis, and is required for sperm head elongation and acrosome formation during spermatogenesis. Mutations in this gene are associated with an infertility disorder, spermatogenic failure type 9 (SPGF9). [provided by RefSeq, Dec 2011]

DPY19L2 links:

DPY19L2 (HGNC:):

DPY19L2 links:

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ACMG classification

Classification made for transcript

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, 0.833

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPY19L2	NM_173812.5 linkuse as main transcript	c.2006G>A	p.Arg669Gln	missense_variant	21/22	ENST00000324472.9	NP_776173.3	Q6NUT2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPY19L2	ENST00000324472.9 linkuse as main transcript	c.2006G>A	p.Arg669Gln	missense_variant	21/22	1	NM_173812.5	ENSP00000315988.4		Q6NUT2-1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

151746

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000599

AC:

AN:

233796

Hom.:

AF XY:

0.0000631

AC XY:

AN XY:

126816

show subpopulations

Gnomad AFR exome

AF:

0.0000663

Gnomad AMR exome

AF:

0.0000998

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000581

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000739

Gnomad OTH exome

AF:

0.000175

GnomAD4 exome

AF:

0.0000799

AC:

114

AN:

1427260

Hom.:

Cov.:

AF XY:

0.0000846

AC XY:

AN XY:

709524

show subpopulations

Gnomad4 AFR exome

AF:

0.0000938

Gnomad4 AMR exome

AF:

0.000127

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000516

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.0000921

Gnomad4 OTH exome

AF:

0.0000340

GnomAD4 genome

AF:

0.000145

AC:

AN:

151746

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74102

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.000159

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2023

The c.2006G>A (p.R669Q) alteration is located in exon 21 (coding exon 21) of the DPY19L2 gene. This alteration results from a G to A substitution at nucleotide position 2006, causing the arginine (R) at amino acid position 669 to be replaced by a glutamine (Q). 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

0.31

BayesDel_addAF

Uncertain

0.029

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.87

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.081

MetaRNN

Pathogenic

0.83

MetaSVM

Uncertain

0.46

MutationAssessor

Pathogenic

3.0

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.6

REVEL

Pathogenic

0.84

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.68

MVP

0.62

MPC

0.77

ClinPred

0.75

GERP RS

3.5

Varity_R

0.57

gMVP

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.22

Position offset: 5

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over