NM_173812.5:c.804-8_804-5dupTTTT

Variant names:

• chr12-63626530-T-TAAAA
• rs371578418
• NM_173812.5:c.804-8_804-5dupTTTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_173812.5(DPY19L2):​c.804-8_804-5dupTTTT 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 0.00024 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0029 (39 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: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000236 (30/127298) while in subpopulation EAS AF = 0.00185 (8/4316). AF 95% confidence interval is 0.000922. There are 0 homozygotes in GnomAd4. There are 19 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

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.804-8_804-5dupTTTT		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_804-4insTTTT		splice_region intron	N/A	ENSP00000315988.4
	DPY19L2	ENST00000306389.7	TSL:1	n.*287-5_*287-4insTTTT		splice_region intron	N/A	ENSP00000445878.1
	ENSG00000249753	ENST00000509615.2	TSL:5	n.239-2707_239-2706insTTTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000236 AC: 30 AN: 127312 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00464

Gnomad AMR AF: 0.000320

Gnomad ASJ AF: 0.000305

Gnomad EAS AF: 0.00185

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00379

Gnomad NFE AF: 0.000193

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00520 AC: 487 AN: 93570 AF XY: 0.00489

Gnomad AFR exome AF: 0.00563

Gnomad AMR exome AF: 0.00693

Gnomad ASJ exome AF: 0.00355

Gnomad EAS exome AF: 0.0188

Gnomad FIN exome AF: 0.00194

Gnomad NFE exome AF: 0.00373

Gnomad OTH exome AF: 0.00686

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00290 AC: 3519 AN: 1212928 Hom.: 39 Cov.: 33 AF XY: 0.00300 AC XY: 1797 AN XY: 599868

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

African (AFR) AF: 0.00149 AC: 37 AN: 24858

American (AMR) AF: 0.00493 AC: 110 AN: 22324

Ashkenazi Jewish (ASJ) AF: 0.00396 AC: 78 AN: 19696

East Asian (EAS) AF: 0.00765 AC: 228 AN: 29798

South Asian (SAS) AF: 0.00606 AC: 377 AN: 62246

European-Finnish (FIN) AF: 0.00273 AC: 109 AN: 39884

Middle Eastern (MID) AF: 0.00207 AC: 9 AN: 4346

European-Non Finnish (NFE) AF: 0.00251 AC: 2409 AN: 960434

Other (OTH) AF: 0.00328 AC: 162 AN: 49342

⚠️ 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: 0.000236 AC: 30 AN: 127298 Hom.: 0 Cov.: 0 AF XY: 0.000313 AC XY: 19 AN XY: 60752

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

American (AMR) AF: 0.000320 AC: 4 AN: 12492

Ashkenazi Jewish (ASJ) AF: 0.000305 AC: 1 AN: 3274

East Asian (EAS) AF: 0.00185 AC: 8 AN: 4316

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6388

Middle Eastern (MID) AF: 0.00413 AC: 1 AN: 242

European-Non Finnish (NFE) AF: 0.000193 AC: 12 AN: 62310

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

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;