Variant 12-63597810-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173812.5(DPY19L2):c.1460C>T(p.Ala487Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,603,140 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. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

DPY19L2
NM_173812.5 missense, splice_region

Scores

Splicing: ADA: 0.002825

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13161567).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPY19L2	NM_173812.5 linkuse as main transcript	c.1460C>T	p.Ala487Val	missense_variant, splice_region_variant	14/22	ENST00000324472.9	NP_776173.3	Q6NUT2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DPY19L2	ENST00000324472.9 linkuse as main transcript	c.1460C>T	p.Ala487Val	missense_variant, splice_region_variant	14/22	1	NM_173812.5	ENSP00000315988.4	Q6NUT2-1
DPY19L2	ENST00000306389.7 linkuse as main transcript	n.*851C>T		splice_region_variant, non_coding_transcript_exon_variant	12/14	1		ENSP00000445878.1	F5H0W1
DPY19L2	ENST00000306389.7 linkuse as main transcript	n.*851C>T		3_prime_UTR_variant	12/14	1		ENSP00000445878.1	F5H0W1
DPY19L2	ENST00000439061.6 linkuse as main transcript	n.239C>T		splice_region_variant, non_coding_transcript_exon_variant	3/11	5		ENSP00000437474.1	H0YF77

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151880

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000122

AC:

AN:

245226

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

132806

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000298

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:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000186

AC:

AN:

1451260

Hom.:

Cov.:

AF XY:

0.0000208

AC XY:

AN XY:

722070

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000228

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000235

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

151880

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74192

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ExAC

AF:

0.00000824

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

Dec 20, 2021

The c.1460C>T (p.A487V) alteration is located in exon 14 (coding exon 14) of the DPY19L2 gene. This alteration results from a C to T substitution at nucleotide position 1460, causing the alanine (A) at amino acid position 487 to be replaced by a valine (V). 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

0.11

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.0048

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.24

M_CAP

Benign

0.0089

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.3

REVEL

Benign

0.050

Sift

Benign

0.097

Sift4G

Benign

0.14

Polyphen

0.064

Vest4

0.18

MVP

0.20

MPC

0.19

ClinPred

0.26

GERP RS

-0.30

Varity_R

0.093

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0028

dbscSNV1_RF

Benign

0.094

SpliceAI score (max)

0.070

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