11-112016758-C-A

Variant summary

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

The NM_001037954.4(DIXDC1):c.1824C>A(p.Asp608Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. D608D) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: DIXDC1 NM_001037954.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.20

Genes affected

DIXDC1 (HGNC:23695): (DIX domain containing 1) The protein encoded by this gene is a positive regulator of the Wnt signaling pathway. The encoded protein is found associated with gamma tubulin at the centrosome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIXDC1	NM_001037954.4	c.1824C>A	p.Asp608Glu	missense_variant	18/20	ENST00000440460.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIXDC1	ENST00000440460.7	c.1824C>A	p.Asp608Glu	missense_variant	18/20	1	NM_001037954.4	P1
DIXDC1	ENST00000615255.1	c.1191C>A	p.Asp397Glu	missense_variant	14/16	1
DIXDC1	ENST00000526500.5	n.820C>A		non_coding_transcript_exon_variant	9/11	2
DIXDC1	ENST00000618522.4	n.1177C>A		non_coding_transcript_exon_variant	12/14	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

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

Dec 17, 2021

The c.1824C>A (p.D608E) alteration is located in exon 18 (coding exon 18) of the DIXDC1 gene. This alteration results from a C to A substitution at nucleotide position 1824, causing the aspartic acid (D) at amino acid position 608 to be replaced by a glutamic acid (E). 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	Uncertain	0.39
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.028	T;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.0071	T
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-0.76	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.69	T
REVEL	Uncertain	0.33
Sift4G	Benign	0.33	T;T
Polyphen		1.0	D;.
Vest4		0.46
MutPred		0.89		Gain of phosphorylation at Y605 (P = 0.0968);.;
MVP		0.70
MPC		0.74
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.38
gMVP		0.69

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: chr11-111887482;