2-67397582-C-T

Variant names:

• chr2-67397582-C-T
• rs191028204
• NM_019002.4:c.134C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_019002.4(ETAA1):​c.134C>T​(p.Pro45Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,558,308 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (1 hom.)
• Consequence: ETAA1 NM_019002.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.95
• Publications: 0 publications found

Genes affected

ETAA1 (HGNC:24648): (ETAA1 activator of ATR kinase) Enables protein serine/threonine kinase activator activity. Involved in several processes, including positive regulation of protein serine/threonine kinase activity; regulation of DNA damage checkpoint; and replication fork processing. Located in cytosol; nuclear replication fork; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LINC01829 (HGNC:52635): (long intergenic non-protein coding RNA 1829)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029494464).
• BP6: Variant 2-67397582-C-T is Benign according to our data. Variant chr2-67397582-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2364403.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019002.4. 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
	ETAA1	NM_019002.4	MANE Select	c.134C>T	p.Pro45Leu	missense	Exon 1 of 6	NP_061875.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETAA1	ENST00000272342.6	TSL:1 MANE Select	c.134C>T	p.Pro45Leu	missense	Exon 1 of 6	ENSP00000272342.5	Q9NY74
	ETAA1	ENST00000925952.1		c.134C>T	p.Pro45Leu	missense	Exon 1 of 6	ENSP00000596011.1
	ETAA1	ENST00000925951.1		c.134C>T	p.Pro45Leu	missense	Exon 1 of 6	ENSP00000596010.1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152108 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00271

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000203 AC: 32 AN: 157400 AF XY: 0.000165

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000782

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00254

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000153 AC: 215 AN: 1406082 Hom.: 1 Cov.: 31 AF XY: 0.000143 AC XY: 99 AN XY: 694290

African (AFR) AF: 0.00 AC: 0 AN: 31984

American (AMR) AF: 0.0000541 AC: 2 AN: 36948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25244

East Asian (EAS) AF: 0.00584 AC: 213 AN: 36492

South Asian (SAS) AF: 0.00 AC: 0 AN: 80072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4960

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1083666

Other (OTH) AF: 0.00 AC: 0 AN: 58174

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152226 Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7 AN XY: 74432

African (AFR) AF: 0.00 AC: 0 AN: 41538

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00271 AC: 14 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000128

ExAC AF: 0.000113 AC: 13

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.087
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.14
DANN	Benign	0.78
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.38	N
PhyloP100		-1.9
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.021
Sift	Benign	0.28	T
Sift4G	Benign	0.23	T
Polyphen		0.0010	B
Vest4		0.071
MVP		0.068
MPC		0.043
ClinPred		0.025	T
GERP RS		-4.8
PromoterAI		-0.069	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.025
gMVP		0.026
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs191028204; hg19: chr2-67624714; COSMIC: COSV55472422;