12-63626530-TA-TAAAAAA

Variant names:

• chr12-63626530-T-TAAAAA
• rs371578418
• NM_173812.5:c.804-9_804-5dupTTTTT

Variant summary

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

The NM_173812.5(DPY19L2):​c.804-9_804-5dupTTTTT 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 0.000024 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00044 (7 hom.)
  • Failed GnomAD Quality Control
• Consequence: DPY19L2 NM_173812.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.702
• Publications: 1 publications found

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

ENSG00000249753 (HGNC:):

ACMG classification

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPY19L2	NM_173812.5	MANE Select	c.804-9_804-5dupTTTTT		splice_region intron	N/A	NP_776173.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPY19L2	ENST00000324472.9	TSL:1 MANE Select	c.804-5_804-4insTTTTT		splice_region intron	N/A	ENSP00000315988.4
	DPY19L2	ENST00000306389.7	TSL:1	n.*287-5_*287-4insTTTTT		splice_region intron	N/A	ENSP00000445878.1
	ENSG00000249753	ENST00000509615.2	TSL:5	n.239-2707_239-2706insTTTTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000236 AC: 3 AN: 127324 Hom.: 0 Cov.: 0

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000481

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00135 AC: 126 AN: 93570 AF XY: 0.00116

Gnomad AFR exome AF: 0.00230

Gnomad AMR exome AF: 0.00171

Gnomad ASJ exome AF: 0.00118

Gnomad EAS exome AF: 0.00527

Gnomad FIN exome AF: 0.000646

Gnomad NFE exome AF: 0.000854

Gnomad OTH exome AF: 0.00214

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000442 AC: 539 AN: 1218802 Hom.: 7 Cov.: 33 AF XY: 0.000468 AC XY: 282 AN XY: 602792

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

African (AFR) AF: 0.000441 AC: 11 AN: 24960

American (AMR) AF: 0.000801 AC: 18 AN: 22460

Ashkenazi Jewish (ASJ) AF: 0.000454 AC: 9 AN: 19802

East Asian (EAS) AF: 0.00146 AC: 44 AN: 30088

South Asian (SAS) AF: 0.00112 AC: 70 AN: 62694

European-Finnish (FIN) AF: 0.000574 AC: 23 AN: 40092

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4366

European-Non Finnish (NFE) AF: 0.000344 AC: 332 AN: 964738

Other (OTH) AF: 0.000645 AC: 32 AN: 49602

⚠️ 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.

GnomAD4 genome AF: 0.0000236 AC: 3 AN: 127310 Hom.: 0 Cov.: 0 AF XY: 0.0000329 AC XY: 2 AN XY: 60760

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

African (AFR) AF: 0.00 AC: 0 AN: 31610

American (AMR) AF: 0.00 AC: 0 AN: 12492

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3274

East Asian (EAS) AF: 0.00 AC: 0 AN: 4318

South Asian (SAS) AF: 0.00 AC: 0 AN: 4090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 242

European-Non Finnish (NFE) AF: 0.0000481 AC: 3 AN: 62318

Other (OTH) AF: 0.00 AC: 0 AN: 1714

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00109982), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.70
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs371578418; hg19: chr12-64020310;