chr2-67397572-G-A

Position:

• chr2-67397572-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019002.4(ETAA1):​c.124G>A​(p.Gly42Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,411,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: ETAA1 NM_019002.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.753

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10402262).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETAA1	NM_019002.4	c.124G>A	p.Gly42Ser	missense_variant	1/6	ENST00000272342.6	NP_061875.2
ETAA1	XM_017004376.2	c.124G>A	p.Gly42Ser	missense_variant	1/7		XP_016859865.1
ETAA1	XM_017004377.2	c.124G>A	p.Gly42Ser	missense_variant	1/7		XP_016859866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETAA1	ENST00000272342.6	c.124G>A	p.Gly42Ser	missense_variant	1/6	1	NM_019002.4	ENSP00000272342.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000496 AC: 7 AN: 1411862 Hom.: 0 Cov.: 31 AF XY: 0.00000430 AC XY: 3 AN XY: 697646

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000120

GnomAD4 genome Cov.: 32

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

Feb 06, 2023

The c.124G>A (p.G42S) alteration is located in exon 1 (coding exon 1) of the ETAA1 gene. This alteration results from a G to A substitution at nucleotide position 124, causing the glycine (G) at amino acid position 42 to be replaced by a serine (S). 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	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0037	T;.
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.6	N;.
REVEL	Benign	0.021
Sift	Benign	0.18	T;.
Sift4G	Benign	0.23	T;.
Polyphen		0.58	P;.
Vest4		0.10
MutPred		0.16		Gain of phosphorylation at G42 (P = 0.0104);Gain of phosphorylation at G42 (P = 0.0104);
MVP		0.082
MPC		0.052
ClinPred		0.24	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.035
gMVP		0.026

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

Publications

LitVar

Other links and lift over

dbSNP: rs1395551276; hg19: chr2-67624704;