12-51242509-T-G

Variant names:

• chr12-51242509-T-G
• NM_014764.4:c.*51T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001136266.2(DAZAP2):​c.481T>G​(p.Phe161Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,268 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/20 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DAZAP2 NM_001136266.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.02
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136266.2. 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.*51T>G		3_prime_UTR	Exon 4 of 4	NP_055579.1	Q15038-1
	DAZAP2	NM_001136266.2		c.481T>G	p.Phe161Val	missense	Exon 4 of 4	NP_001129738.1	Q15038-5
	DAZAP2	NM_001136264.2		c.*51T>G		3_prime_UTR	Exon 5 of 5	NP_001129736.1	Q15038-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAZAP2	ENST00000412716.8	TSL:1 MANE Select	c.*51T>G		3_prime_UTR	Exon 4 of 4	ENSP00000394699.2	Q15038-1
	DAZAP2	ENST00000549555.5	TSL:2	c.481T>G	p.Phe161Val	missense	Exon 4 of 4	ENSP00000448051.1	Q15038-5
	DAZAP2	ENST00000551313.1	TSL:3	c.*51T>G		splice_region	Exon 4 of 4	ENSP00000447842.1	F8VUW5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461268 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 726982

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5260

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60338

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	Benign	0.32
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	17
DANN	Uncertain	0.99
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.88	T
PhyloP100		3.0
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Vest4		0.67
MutPred		0.20		Gain of sheet (P = 0.039)
MVP		0.44
MPC		1.4
ClinPred		0.77	D
GERP RS		4.9
gMVP		0.21
Mutation Taster		=79/21	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: chr12-51636293;