2-27215633-A-G

Position:

• chr2-27215633-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The ENST00000380171.9(ATRAID):​c.367A>G​(p.Ile123Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ATRAID ENST00000380171.9 missense, splice_region
• Scores: Splicing: ADA: 0.00007483
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0370

Genes affected

ATRAID (HGNC:24090): (all-trans retinoic acid induced differentiation factor) This gene is thought to be involved in apoptosis, and may also be involved in hematopoietic development and differentiation. The use of alternative splice sites and promotors result in multiple transcript variants encoding different isoforms.[provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12039116).
• BP6: Variant 2-27215633-A-G is Benign according to our data. Variant chr2-27215633-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3332387.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATRAID	NM_001170795.4	c.367A>G	p.Ile123Val	missense_variant, splice_region_variant	5/7	ENST00000380171.9	NP_001164266.1
ATRAID	NM_016085.5	c.193A>G	p.Ile65Val	missense_variant, splice_region_variant	5/7		NP_057169.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATRAID	ENST00000380171.9	c.367A>G	p.Ile123Val	missense_variant, splice_region_variant	5/7	1	NM_001170795.4	ENSP00000369518.4
ATRAID	ENST00000405489.7	c.193A>G	p.Ile65Val	missense_variant, splice_region_variant	5/7	1		ENSP00000384033.3
ATRAID	ENST00000419744.1	c.193A>G	p.Ile65Val	missense_variant, splice_region_variant	4/4	2		ENSP00000397319.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 06, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.0
DANN	Benign	0.63
DEOGEN2	Benign	0.0059	.;.;T;.;T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.53	.;T;T;T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	.;.;M;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.030	N;.;.;N;N
REVEL	Benign	0.037
Sift	Benign	0.23	T;.;.;T;T
Sift4G	Benign	0.51	T;T;T;T;T
Polyphen		0.049	B;B;B;.;.
Vest4		0.081
MutPred		0.24		.;.;Loss of catalytic residue at P125 (P = 0.0386);.;.;
MVP		0.27
MPC		0.057
ClinPred		0.052	T
GERP RS		-2.8
Varity_R		0.0099
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000075
dbscSNV1_RF	Benign	0.018
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-27438501;