20-18384491-C-A

Variant names:

• chr20-18384491-C-A
• rs752231081
• NM_001367614.1:c.2242G>T

Variant summary

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

The NM_001367614.1(DZANK1):​c.2242G>T​(p.Asp748Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DZANK1 NM_001367614.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.65
• Publications: 1 publications found

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]

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=0.30024153).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367614.1. 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
	DZANK1	NM_001367614.1	MANE Select	c.2242G>T	p.Asp748Tyr	missense	Exon 21 of 21	NP_001354543.1	A0A8V8TNE5
	DZANK1	NM_001367617.1		c.2242G>T	p.Asp748Tyr	missense	Exon 21 of 21	NP_001354546.1	A0A8V8TNE5
	DZANK1	NM_001367618.1		c.2242G>T	p.Asp748Tyr	missense	Exon 21 of 21	NP_001354547.1	A0A8V8TNE5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DZANK1	ENST00000699568.1	MANE Select	c.2242G>T	p.Asp748Tyr	missense	Exon 21 of 21	ENSP00000514442.1	A0A8V8TNE5
	DZANK1	ENST00000699590.1		c.2200G>T	p.Asp734Tyr	missense	Exon 21 of 21	ENSP00000514461.1	A0A8V8TPU7
	DZANK1	ENST00000699525.1		c.2185G>T	p.Asp729Tyr	missense	Exon 21 of 21	ENSP00000514418.1	A0A8V8TNH6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459788 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725920

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26034

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 85644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111148

Other (OTH) AF: 0.00 AC: 0 AN: 60326

GnomAD4 genome Cov.: 31

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	0.092
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.6
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.16
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.91	P
Vest4		0.26
MutPred		0.54		Loss of disorder (P = 0.1335)
MVP		0.35
MPC		0.14
ClinPred		0.97	D
GERP RS		3.5
Varity_R		0.24
gMVP		0.39
Mutation Taster		=91/9	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: rs752231081; hg19: chr20-18365135;