chr10-73134617-T-G

Variant names:

• chr10-73134617-T-G
• rs2271904
• NM_007265.3:c.1901A>C

Variant summary

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

The NM_007265.3(ECD):​c.1901A>C​(p.Asp634Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ECD NM_007265.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.68
• Publications: 41 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECD	NM_007265.3	c.1901A>C	p.Asp634Ala	missense_variant	Exon 14 of 14	ENST00000372979.9	NP_009196.1
ECD	NM_001135752.1	c.2000A>C	p.Asp667Ala	missense_variant	Exon 15 of 15		NP_001129224.1
ECD	NM_001135753.1	c.1772A>C	p.Asp591Ala	missense_variant	Exon 13 of 13		NP_001129225.1
ECD	NR_024203.1	n.1733A>C		non_coding_transcript_exon_variant	Exon 12 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECD	ENST00000372979.9	c.1901A>C	p.Asp634Ala	missense_variant	Exon 14 of 14	1	NM_007265.3	ENSP00000362070.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2298

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;.;.
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Benign	-0.69	T
PhyloP100		6.7
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-5.1	D;D;D
REVEL	Benign	0.21
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.39
MutPred		0.27		Gain of MoRF binding (P = 0.047);.;.;
MVP		0.65
MPC		0.46
ClinPred		0.99	D
GERP RS		5.7
PromoterAI		-0.014	Neutral
Varity_R		0.53
gMVP		0.56
Mutation Taster		=70/30	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: rs2271904; hg19: chr10-74894375;