12-51242334-C-T

Variant names:

• chr12-51242334-C-T
• rs549110284
• NM_014764.4:c.383C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_014764.4(DAZAP2):​c.383C>T​(p.Pro128Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000566 in 1,589,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000058 (0 hom.)
• Consequence: DAZAP2 NM_014764.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.33
• Publications: 1 publications found

Genes affected

DAZAP2 (HGNC:2684): (DAZ associated protein 2) This gene encodes a proline-rich protein which interacts with the deleted in azoospermia (DAZ) and the deleted in azoospermia-like gene through the DAZ-like repeats. This protein also interacts with the transforming growth factor-beta signaling molecule SARA (Smad anchor for receptor activation), eukaryotic initiation factor 4G, and an E3 ubiquitinase that regulates its stability in splicing factor containing nuclear speckles. The encoded protein may function in various biological and pathological processes including spermatogenesis, cell signaling and transcription regulation, formation of stress granules during translation arrest, RNA splicing, and pathogenesis of multiple myeloma. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.26316625).
• BP6: Variant 12-51242334-C-T is Benign according to our data. Variant chr12-51242334-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3270910.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014764.4. 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
	DAZAP2	NM_014764.4	MANE Select	c.383C>T	p.Pro128Leu	missense	Exon 4 of 4	NP_055579.1	Q15038-1
	DAZAP2	NM_001136264.2		c.317C>T	p.Pro106Leu	missense	Exon 5 of 5	NP_001129736.1	Q15038-6
	DAZAP2	NM_001136267.2		c.287C>T	p.Pro96Leu	missense	Exon 4 of 4	NP_001129739.1	Q15038-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAZAP2	ENST00000412716.8	TSL:1 MANE Select	c.383C>T	p.Pro128Leu	missense	Exon 4 of 4	ENSP00000394699.2	Q15038-1
	DAZAP2	ENST00000449723.7	TSL:5	c.317C>T	p.Pro106Leu	missense	Exon 5 of 5	ENSP00000412812.2	Q15038-6
	DAZAP2	ENST00000549732.6	TSL:2	c.287C>T	p.Pro96Leu	missense	Exon 4 of 4	ENSP00000446554.2	Q15038-3

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152144 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: 0.000770

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.0000730 AC: 17 AN: 232790 AF XY: 0.0000636

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000610

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000939

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000577 AC: 83 AN: 1437732 Hom.: 0 Cov.: 29 AF XY: 0.0000603 AC XY: 43 AN XY: 713156

African (AFR) AF: 0.00 AC: 0 AN: 32748

American (AMR) AF: 0.00 AC: 0 AN: 41034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24358

East Asian (EAS) AF: 0.00111 AC: 44 AN: 39464

South Asian (SAS) AF: 0.000169 AC: 14 AN: 82990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5648

European-Non Finnish (NFE) AF: 0.0000200 AC: 22 AN: 1099656

Other (OTH) AF: 0.0000506 AC: 3 AN: 59340

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152262 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74430

African (AFR) AF: 0.00 AC: 0 AN: 41556

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000659 AC: 8

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	0.058	D
PhyloP100		5.3
PROVEAN	Pathogenic	-7.0	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.54
MutPred		0.45		Loss of glycosylation at P128 (P = 0.0061)
MVP		0.67
ClinPred		0.39	T
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.68
Mutation Taster		=11/89	disease causing

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: rs549110284; hg19: chr12-51636118; COSMIC: COSV66312829; COSMIC: COSV66312829;