chr12-63595971-T-C

Variant names:

• chr12-63595971-T-C
• NM_173812.5:c.1528A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173812.5(DPY19L2):​c.1528A>G​(p.Lys510Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DPY19L2 NM_173812.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.52
• 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4163463).

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.1528A>G	p.Lys510Glu	missense	Exon 15 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.1528A>G	p.Lys510Glu	missense	Exon 15 of 22	ENSP00000315988.4	Q6NUT2-1
	DPY19L2	ENST00000306389.7	TSL:1	n.*919A>G		non_coding_transcript_exon	Exon 13 of 14	ENSP00000445878.1	F5H0W1
	DPY19L2	ENST00000306389.7	TSL:1	n.*919A>G		3_prime_UTR	Exon 13 of 14	ENSP00000445878.1	F5H0W1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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	Benign	0.16
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0067	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.89	T
PhyloP100		2.5
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.22
Sift	Benign	0.35	T
Sift4G	Benign	0.28	T
Polyphen		0.66	P
Vest4		0.49
MutPred		0.62		Loss of methylation at K510 (P = 0.0114)
MVP		0.28
MPC		0.34
ClinPred		0.74	D
GERP RS		3.8
Varity_R		0.15
gMVP		0.48
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

hg19: chr12-63989751;