Variant 12-63597906-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_173812.5(DPY19L2):c.1364G>T(p.Arg455Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,588,958 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 19 hom. )

Consequence

DPY19L2
NM_173812.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.79

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0106499195).

BP6

Variant 12-63597906-C-A is Benign according to our data. Variant chr12-63597906-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3388024.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00162 (246/151838) while in subpopulation SAS AF= 0.00706 (34/4818). AF 95% confidence interval is 0.00519. There are 3 homozygotes in gnomad4. There are 119 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPY19L2	NM_173812.5 linkuse as main transcript	c.1364G>T	p.Arg455Leu	missense_variant	14/22	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.1364G>T	p.Arg455Leu	missense_variant	14/22	1	NM_173812.5	ENSP00000315988.4		Q6NUT2-1

Frequencies

GnomAD3 genomes

AF:

0.00163

AC:

247

AN:

151720

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000363

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00446

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00726

Gnomad FIN

AF:

0.0000953

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00147

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00212

AC:

496

AN:

233582

Hom.:

AF XY:

0.00239

AC XY:

303

AN XY:

127042

show subpopulations

Gnomad AFR exome

AF:

0.000269

Gnomad AMR exome

AF:

0.00192

Gnomad ASJ exome

AF:

0.00856

Gnomad EAS exome

AF:

0.0000577

Gnomad SAS exome

AF:

0.00744

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00126

Gnomad OTH exome

AF:

0.00306

GnomAD4 exome

AF:

0.00178

AC:

2561

AN:

1437120

Hom.:

Cov.:

AF XY:

0.00194

AC XY:

1387

AN XY:

714976

show subpopulations

Gnomad4 AFR exome

AF:

0.000435

Gnomad4 AMR exome

AF:

0.00222

Gnomad4 ASJ exome

AF:

0.00796

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00774

Gnomad4 FIN exome

AF:

0.0000944

Gnomad4 NFE exome

AF:

0.00133

Gnomad4 OTH exome

AF:

0.00246

GnomAD4 genome

AF:

0.00162

AC:

246

AN:

151838

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

119

AN XY:

74190

show subpopulations

Gnomad4 AFR

AF:

0.000362

Gnomad4 AMR

AF:

0.00446

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00706

Gnomad4 FIN

AF:

0.0000953

Gnomad4 NFE

AF:

0.00147

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00172

Hom.:

Bravo

AF:

0.00190

ESP6500AA

AF:

0.000456

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.00199

AC:

241

Asia WGS

AF:

0.00261

AC:

AN:

3466

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

DPY19L2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.064

T;T

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.41

T;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0090

D;D

Sift4G

Uncertain

0.0080

D;.

Polyphen

0.013

B;.

Vest4

0.38

MVP

0.43

MPC

0.22

ClinPred

0.028

GERP RS

0.055

Varity_R

0.11

gMVP

0.71

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.

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