10-73134727-G-T

Position:

• chr10-73134727-G-T

Variant summary

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

The NM_007265.3(ECD):​c.1791C>A​(p.Asp597Glu) 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ECD NM_007265.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.819

Genes affected

ECD (HGNC:17029): (ecdysoneless cell cycle regulator) Enables histone acetyltransferase binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ECD (HGNC:):

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	Protein	UniProt
ECD	NM_007265.3	c.1791C>A	p.Asp597Glu	missense_variant	14/14	ENST00000372979.9	NP_009196.1
ECD	NM_001135752.1	c.1890C>A	p.Asp630Glu	missense_variant	15/15		NP_001129224.1
ECD	NM_001135753.1	c.1662C>A	p.Asp554Glu	missense_variant	13/13		NP_001129225.1
ECD	NR_024203.1	n.1623C>A		non_coding_transcript_exon_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECD	ENST00000372979.9	c.1791C>A	p.Asp597Glu	missense_variant	14/14	1	NM_007265.3	ENSP00000362070.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251462 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135904

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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

Jul 14, 2021

The c.1890C>A (p.D630E) alteration is located in exon 15 (coding exon 14) of the ECD gene. This alteration results from a C to A substitution at nucleotide position 1890, causing the aspartic acid (D) at amino acid position 630 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	0.50
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;.;.
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Benign	-0.82	T
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Uncertain	0.38
Sift	Benign	0.032	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.75	P;.;.
Vest4		0.46
MutPred		0.89		Gain of sheet (P = 0.1208);.;.;
MVP		0.46
MPC		0.20
ClinPred		0.96	D
GERP RS		3.5
Varity_R		0.42
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201794246; hg19: chr10-74894485;