20-18384410-C-G

Position:

• chr20-18384410-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001367614.1(DZANK1):​c.2323G>C​(p.Asp775His) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: DZANK1 NM_001367614.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.19

Genes affected

DZANK1 (HGNC:15858): (double zinc ribbon and ankyrin repeat domains 1) This gene contains two ankyrin repeat-encoding regions. Ankyrin repeats are tandemly repeated modules of about 33 amino acids described as L-shaped structures consisting of a beta-hairpin and two alpha-helices. Ankyrin repeats occur in a large number of functionally diverse proteins, mainly from eukaryotes, and are known to function as protein-protein interaction domains. [provided by RefSeq, Dec 2018]

DZANK1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20000839).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DZANK1	NM_001367614.1	c.2323G>C	p.Asp775His	missense_variant	21/21	ENST00000699568.1	NP_001354543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DZANK1	ENST00000699568.1	c.2323G>C	p.Asp775His	missense_variant	21/21		NM_001367614.1	ENSP00000514442.1
DZANK1	ENST00000699590.1	c.2281G>C	p.Asp761His	missense_variant	21/21			ENSP00000514461.1
DZANK1	ENST00000699525.1	c.2266G>C	p.Asp756His	missense_variant	21/21			ENSP00000514418.1
DZANK1	ENST00000357236.8	c.1669G>C	p.Asp557His	missense_variant	17/17	5		ENSP00000349774.5
DZANK1	ENST00000377630.9	n.*1454G>C		non_coding_transcript_exon_variant	20/20	2		ENSP00000366857.6
DZANK1	ENST00000377630.9	n.*1454G>C		3_prime_UTR_variant	20/20	2		ENSP00000366857.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2024

The c.2248G>C (p.D750H) alteration is located in exon 21 (coding exon 20) of the DZANK1 gene. This alteration results from a G to C substitution at nucleotide position 2248, causing the aspartic acid (D) at amino acid position 750 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0034	T;T;T;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.76	T;T;.;T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.20	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.;L;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.4	N;.;.;.
REVEL	Benign	0.11
Sift	Uncertain	0.015	D;.;.;.
Sift4G	Benign	0.11	T;T;T;T
Polyphen		0.84	P;.;P;.
Vest4		0.18
MutPred		0.44		Loss of stability (P = 0.0731);.;Loss of stability (P = 0.0731);.;
MVP		0.45
MPC		0.18
ClinPred		0.81	D
GERP RS		3.5
Varity_R		0.077
gMVP		0.46

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-18365054;