rs371578418

Positions:

• chr12-63626530-TA-T
• chr12-63626530-TA-TAA
• chr12-63626530-TA-TAAA
• chr12-63626530-TA-TAAAA
• chr12-63626530-TA-TAAAAA
• chr12-63626530-TA-TAAAAAA
• chr12-63626530-TA-TAAAAAAA
• chr12-63626530-TA-TAAAAAAAA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_173812.5(DPY19L2):​c.804-5del variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.702

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000185 (225/1218602) while in subpopulation AMR AF= 0.00125 (28/22432). AF 95% confidence interval is 0.000887. There are 0 homozygotes in gnomad4_exome. There are 113 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPY19L2	NM_173812.5	c.804-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000324472.9	NP_776173.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPY19L2	ENST00000324472.9	c.804-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_173812.5	ENSP00000315988	P1
DPY19L2	ENST00000306389.7	c.*287-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		1		ENSP00000445878
	ENST00000509615.2	n.239-2707del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0000314 AC: 4 AN: 127322 Hom.: 0 Cov.: 0

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.: 0 Cov.: 33 AF XY: 0.000187 AC XY: 113 AN XY: 602722

Gnomad4 AFR exome AF: 0.000240

Gnomad4 AMR exome AF: 0.00125

Gnomad4 ASJ exome AF: 0.000454

Gnomad4 EAS exome AF: 0.000133

Gnomad4 SAS exome AF: 0.000574

Gnomad4 FIN exome AF: 0.000325

Gnomad4 NFE exome AF: 0.000121

Gnomad4 OTH exome AF: 0.000222

GnomAD4 genome AF: 0.0000314 AC: 4 AN: 127322 Hom.: 0 Cov.: 0 AF XY: 0.0000165 AC XY: 1 AN XY: 60746

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000801

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000157

Gnomad4 NFE AF: 0.0000160

Gnomad4 OTH AF: 0.000587

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs371578418; hg19: chr12-64020310;