rs2271904

Variant names:

• chr10-73134617-T-C
• rs2271904
• NM_007265.3:c.1901A>G
• ECD p.Asp634Gly

Your query was ambiguous. Multiple possible variants found:

• chr10-73134617-T-C
• chr10-73134617-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007265.3(ECD):​c.1901A>G​(p.Asp634Gly) variant causes a missense change. The variant allele was found at a frequency of 0.083 in 1,614,064 control chromosomes in the GnomAD database, including 8,384 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.10 (1238 hom., cov: 32)
  • Exomes 𝑓: 0.081 (7146 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017505586).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007265.3. 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
	ECD	NM_007265.3	MANE Select	c.1901A>G	p.Asp634Gly	missense	Exon 14 of 14	NP_009196.1	O95905-1
	ECD	NM_001135752.1		c.2000A>G	p.Asp667Gly	missense	Exon 15 of 15	NP_001129224.1	O95905-3
	ECD	NM_001135753.1		c.1772A>G	p.Asp591Gly	missense	Exon 13 of 13	NP_001129225.1	O95905-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECD	ENST00000372979.9	TSL:1 MANE Select	c.1901A>G	p.Asp634Gly	missense	Exon 14 of 14	ENSP00000362070.4	O95905-1
	ECD	ENST00000430082.6	TSL:1	c.2000A>G	p.Asp667Gly	missense	Exon 15 of 15	ENSP00000401566.1	O95905-3
	ECD	ENST00000454759.6	TSL:1	c.1772A>G	p.Asp591Gly	missense	Exon 13 of 13	ENSP00000395786.1	O95905-2

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15923 AN: 152140 Hom.: 1218 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0882

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.0411

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0607

Gnomad OTH AF: 0.0938

GnomAD2 exomes AF: 0.110 AC: 27648 AN: 251416 AF XY: 0.113

Gnomad AFR exome AF: 0.161

Gnomad AMR exome AF: 0.0857

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.306

Gnomad FIN exome AF: 0.0437

Gnomad NFE exome AF: 0.0609

Gnomad OTH exome AF: 0.0851

GnomAD4 exome AF: 0.0807 AC: 117965 AN: 1461806 Hom.: 7146 Cov.: 31 AF XY: 0.0846 AC XY: 61522 AN XY: 727208

African (AFR) AF: 0.165 AC: 5537 AN: 33474

American (AMR) AF: 0.0867 AC: 3878 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 2900 AN: 26136

East Asian (EAS) AF: 0.280 AC: 11119 AN: 39698

South Asian (SAS) AF: 0.222 AC: 19135 AN: 86244

European-Finnish (FIN) AF: 0.0451 AC: 2407 AN: 53420

Middle Eastern (MID) AF: 0.0751 AC: 433 AN: 5766

European-Non Finnish (NFE) AF: 0.0602 AC: 66917 AN: 1111956

Other (OTH) AF: 0.0934 AC: 5639 AN: 60394

GnomAD4 genome AF: 0.105 AC: 15983 AN: 152258 Hom.: 1238 Cov.: 32 AF XY: 0.107 AC XY: 7985 AN XY: 74454

African (AFR) AF: 0.161 AC: 6686 AN: 41546

American (AMR) AF: 0.0882 AC: 1349 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 389 AN: 3470

East Asian (EAS) AF: 0.304 AC: 1574 AN: 5184

South Asian (SAS) AF: 0.230 AC: 1109 AN: 4822

European-Finnish (FIN) AF: 0.0411 AC: 436 AN: 10616

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0608 AC: 4132 AN: 68014

Other (OTH) AF: 0.0961 AC: 203 AN: 2112

Alfa AF: 0.0810 Hom.: 2298

Bravo AF: 0.108

Asia WGS AF: 0.259 AC: 898 AN: 3478

EpiCase AF: 0.0610

EpiControl AF: 0.0600

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.0	T
PhyloP100		6.7
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.19
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0070	D
PromoterAI		-0.018	Neutral
Varity_R		0.55
gMVP		0.47
Mutation Taster		=91/9	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2271904;

hg19: chr10-74894375;

COSMIC: COSV61968330;

COSMIC: COSV61968330;