2-67397531-C-G

Variant names:

• chr2-67397531-C-G
• rs200411178
• NM_019002.4:c.83C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019002.4(ETAA1):​c.83C>G​(p.Ser28Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000252 in 1,588,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S28L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ETAA1 NM_019002.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.434
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19139993).

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.83C>G	p.Ser28Trp	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.83C>G	p.Ser28Trp	missense	Exon 1 of 6	ENSP00000272342.5	Q9NY74
	ETAA1	ENST00000925952.1		c.83C>G	p.Ser28Trp	missense	Exon 1 of 6	ENSP00000596011.1
	ETAA1	ENST00000925951.1		c.83C>G	p.Ser28Trp	missense	Exon 1 of 6	ENSP00000596010.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152146 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: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000209 AC: 3 AN: 1436178 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 712006

African (AFR) AF: 0.00 AC: 0 AN: 32888

American (AMR) AF: 0.00 AC: 0 AN: 41346

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25706

East Asian (EAS) AF: 0.00 AC: 0 AN: 38374

South Asian (SAS) AF: 0.00 AC: 0 AN: 82886

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 0.00000273 AC: 3 AN: 1099670

Other (OTH) AF: 0.00 AC: 0 AN: 59338

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152146 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74298

African (AFR) AF: 0.00 AC: 0 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.43
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.10
Sift	Benign	0.039	D
Sift4G	Uncertain	0.023	D
Polyphen		0.10	B
Vest4		0.30
MutPred		0.20		Loss of phosphorylation at S28 (P = 0.0324)
MVP		0.24
MPC		0.052
ClinPred		0.73	D
GERP RS		1.2
PromoterAI		0.00080	Neutral
Varity_R		0.060
gMVP		0.050
Mutation Taster		=96/4	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: rs200411178; hg19: chr2-67624663;