Genetic Variant NM_173812.5:c.804-5delT (chr12-63626530-TA-T) – 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.804-5delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,345,924 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000031 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00018 ( 0 hom. )

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

DPY19L2 links:

ENSG00000249753 (HGNC:):

ENSG00000249753 links:

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ACMG classification

Classification was made for transcript

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

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.804-5delT		splice_region intron	N/A	NP_776173.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DPY19L2	ENST00000324472.9	TSL:1 MANE Select	c.804-5delT	splice_region intron	N/A	ENSP00000315988.4	Q6NUT2-1
DPY19L2	ENST00000306389.7	TSL:1	n.*287-5delT	splice_region intron	N/A	ENSP00000445878.1	F5H0W1
DPY19L2	ENST00000882292.1		c.804-5delT	splice_region intron	N/A	ENSP00000552351.1

Frequencies

GnomAD3 genomes

AF:

0.0000314

AC:

AN:

127322

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000801

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000157

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000160

Gnomad OTH

AF:

0.000587

GnomAD4 exome

AF:

0.000185

AC:

225

AN:

1218602

Hom.:

Cov.:

AF XY:

0.000187

AC XY:

113

AN XY:

602722

show subpopulations

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

African (AFR)

AF:

0.000240

AC:

AN:

24964

American (AMR)

AF:

0.00125

AC:

AN:

22432

Ashkenazi Jewish (ASJ)

AF:

0.000454

AC:

AN:

19806

East Asian (EAS)

AF:

0.000133

AC:

AN:

30104

South Asian (SAS)

AF:

0.000574

AC:

AN:

62752

European-Finnish (FIN)

AF:

0.000325

AC:

AN:

40030

Middle Eastern (MID)

AF:

0.000229

AC:

AN:

4366

European-Non Finnish (NFE)

AF:

0.000121

AC:

117

AN:

964554

Other (OTH)

AF:

0.000222

AC:

AN:

49594

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 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: 0.257

Heterozygous variant carriers

105

140

175

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:

0.0000314

AC:

AN:

127322

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

60746

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:

0.0000801

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:

0.00

AC:

AN:

4112

European-Finnish (FIN)

AF:

0.000157

AC:

AN:

6388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.0000160

AC:

AN:

62328

Other (OTH)

AF:

0.000587

AC:

AN:

1704

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0954766), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.363

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.70

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over