chr12-63569286-T-A

Variant names:

• chr12-63569286-T-A
• rs750515445
• NM_173812.5:c.2064A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_173812.5(DPY19L2):​c.2064A>T​(p.Lys688Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000924 in 1,601,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000095 (0 hom.)
• Consequence: DPY19L2 NM_173812.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.836
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0601615).

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.2064A>T	p.Lys688Asn	missense	Exon 21 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.2064A>T	p.Lys688Asn	missense	Exon 21 of 22	ENSP00000315988.4	Q6NUT2-1
	DPY19L2	ENST00000882292.1		c.2004A>T	p.Lys668Asn	missense	Exon 20 of 21	ENSP00000552351.1
	DPY19L2	ENST00000961037.1		c.1992A>T	p.Lys664Asn	missense	Exon 19 of 20	ENSP00000631096.1

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152108 Hom.: 0 Cov.: 32

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: 0.000132

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000700 AC: 17 AN: 242782 AF XY: 0.0000837

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000613

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000135

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000952 AC: 138 AN: 1449524 Hom.: 0 Cov.: 30 AF XY: 0.0000999 AC XY: 72 AN XY: 720688

African (AFR) AF: 0.00 AC: 0 AN: 33084

American (AMR) AF: 0.0000688 AC: 3 AN: 43614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25910

East Asian (EAS) AF: 0.00 AC: 0 AN: 39180

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83468

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53022

Middle Eastern (MID) AF: 0.000243 AC: 1 AN: 4112

European-Non Finnish (NFE) AF: 0.000118 AC: 131 AN: 1107334

Other (OTH) AF: 0.0000334 AC: 2 AN: 59800

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152108 Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6 AN XY: 74300

African (AFR) AF: 0.00 AC: 0 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 67992

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.000310 Hom.: 0

Bravo AF: 0.0000604

ExAC AF: 0.0000989 AC: 12

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	0.25
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.2
DANN	Benign	0.77
DEOGEN2	Benign	0.00047	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.56	N
PhyloP100		-0.84
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.12
Sift	Benign	0.43	T
Sift4G	Benign	0.51	T
Polyphen		0.0020	B
Vest4		0.24
MutPred		0.57		Gain of catalytic residue at L692 (P = 0.0026)
MVP		0.088
MPC		0.21
ClinPred		0.16	T
GERP RS		-7.0
Varity_R		0.054
gMVP		0.75
Mutation Taster		=92/8	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

dbSNP: rs750515445; hg19: chr12-63963066;