Genetic Variant DPY19L2:c.804-11_804-5dupTTTTTTT (chr12-63626530-T-TAAAAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_173812.5(DPY19L2):c.804-11_804-5dupTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000079 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000020 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

DPY19L2
NM_173812.5 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.702

Publications

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

DPY19L2 links:

ENSG00000249753 (HGNC:):

ENSG00000249753 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPY19L2	NM_173812.5 link	c.804-11_804-5dupTTTTTTT		splice_region_variant, intron_variant	Intron 6 of 21	ENST00000324472.9	NP_776173.3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
DPY19L2	ENST00000324472.9 link	c.804-5_804-4insTTTTTTT	splice_region_variant, intron_variant	Intron 6 of 21	1	NM_173812.5	ENSP00000315988.4
DPY19L2	ENST00000306389.7 link	n.287-5_287-4insTTTTTTT	splice_region_variant, intron_variant	Intron 5 of 13	1		ENSP00000445878.1
ENSG00000249753	ENST00000509615.2 link	n.239-2707_239-2706insTTTTTTT	intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.00000785

AC:

AN:

127322

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000243

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000205

AC:

AN:

1220314

Hom.:

Cov.:

AF XY:

0.0000265

AC XY:

AN XY:

603614

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000400

AC:

AN:

24974

American (AMR)

AF:

0.0000888

AC:

AN:

22524

Ashkenazi Jewish (ASJ)

AF:

0.0000504

AC:

AN:

19832

East Asian (EAS)

AF:

0.000133

AC:

AN:

30148

South Asian (SAS)

AF:

0.0000477

AC:

AN:

62924

European-Finnish (FIN)

AF:

0.0000498

AC:

AN:

40138

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4366

European-Non Finnish (NFE)

AF:

0.0000124

AC:

AN:

965748

Other (OTH)

AF:

0.00

AC:

AN:

49660

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000371843), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.338

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

AF:

0.00000785

AC:

AN:

127322

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

60744

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31568

American (AMR)

AF:

0.00

AC:

AN:

12490

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3274

East Asian (EAS)

AF:

0.00

AC:

AN:

4332

South Asian (SAS)

AF:

0.000243

AC:

AN:

4112

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

62328

Other (OTH)

AF:

0.00

AC:

AN:

1704

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.70

Splicing

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

Publications

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12-63626530-TA-TAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over