Genetic Variant DPY19L2:p.Ile593Val (chr12-63580785-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173812.5(DPY19L2):c.1777A>G(p.Ile593Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

DPY19L2
NM_173812.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.857

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

spermatogenic failure 9
Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
male infertility due to globozoospermia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DPY19L2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12291658).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173812.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPY19L2	NM_173812.5	MANE Select	c.1777A>G	p.Ile593Val	missense	Exon 19 of 22	NP_776173.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DPY19L2	ENST00000324472.9	TSL:1 MANE Select	c.1777A>G	p.Ile593Val	missense	Exon 19 of 22	ENSP00000315988.4	Q6NUT2-1
DPY19L2	ENST00000882292.1		c.1717A>G	p.Ile573Val	missense	Exon 18 of 21	ENSP00000552351.1
DPY19L2	ENST00000961037.1		c.1705A>G	p.Ile569Val	missense	Exon 17 of 20	ENSP00000631096.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000239

AC:

AN:

250656

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000530

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461300

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726958

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.0000224

AC:

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86202

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1111648

Other (OTH)

AF:

0.0000331

AC:

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.0014

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.53

M_CAP

Benign

0.015

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

0.86

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.55

REVEL

Benign

0.047

Sift

Benign

0.46

Sift4G

Benign

0.30

Polyphen

0.035

Vest4

0.24

MVP

0.32

MPC

0.15

ClinPred

0.028

GERP RS

-0.94

Varity_R

0.043

gMVP

0.42

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over