rs147579680

Variant names:

• chr12-63624124-C-G
• rs147579680
• NM_173812.5:c.869G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-63624124-C-G
• chr12-63624124-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PM5 PP3_Moderate

The NM_173812.5(DPY19L2):​c.869G>C​(p.Arg290Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R290H) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DPY19L2 NM_173812.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.68
• Publications: 0 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• male infertility due to globozoospermia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000249753 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr12-63624124-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 101504.Status of the report is no_assertion_criteria_provided, 0 stars.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.883

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.869G>C	p.Arg290Pro	missense	Exon 8 of 22	NP_776173.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPY19L2	ENST00000324472.9	TSL:1 MANE Select	c.869G>C	p.Arg290Pro	missense	Exon 8 of 22	ENSP00000315988.4	Q6NUT2-1
	DPY19L2	ENST00000306389.7	TSL:1	n.*344+2345G>C		intron	N/A	ENSP00000445878.1	F5H0W1
	DPY19L2	ENST00000882292.1		c.869G>C	p.Arg290Pro	missense	Exon 8 of 21	ENSP00000552351.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.74	T
PhyloP100		5.7
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-5.9	D
REVEL	Uncertain	0.62
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.97
MutPred		0.70		Gain of catalytic residue at H285 (P = 0)
MVP		0.66
MPC		2.6
ClinPred		0.99	D
GERP RS		2.8
Varity_R		0.88
gMVP		0.96
Mutation Taster		=32/68	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs147579680; hg19: chr12-64017904;