2-27212447-A-G

Variant names:

• chr2-27212447-A-G
• rs1674616852
• NM_001170795.4:c.79A>G

Variant summary

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

The NM_001170795.4(ATRAID):​c.79A>G​(p.Arg27Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000113 in 1,411,086 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: 34)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: ATRAID NM_001170795.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.447

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]

SLC5A6 (HGNC:11041): (solute carrier family 5 member 6) Enables biotin transmembrane transporter activity and pantothenate transmembrane transporter activity. Involved in anion transmembrane transport and transport across blood-brain barrier. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.15843579).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATRAID	NM_001170795.4	c.79A>G	p.Arg27Gly	missense_variant	Exon 1 of 7	ENST00000380171.9	NP_001164266.1
SLC5A6	NM_021095.4	c.-635T>C		upstream_gene_variant		ENST00000310574.8	NP_066918.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATRAID	ENST00000380171.9	c.79A>G	p.Arg27Gly	missense_variant	Exon 1 of 7	1	NM_001170795.4	ENSP00000369518.4
SLC5A6	ENST00000310574.8	c.-635T>C		upstream_gene_variant		1	NM_021095.4	ENSP00000310208.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.0000113 AC: 16 AN: 1411086 Hom.: 0 Cov.: 77 AF XY: 0.00000860 AC XY: 6 AN XY: 697756

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000275

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000110

Gnomad4 OTH exome AF: 0.0000513

GnomAD4 genome Cov.: 34

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 07, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.244A>G (p.R82G) alteration is located in exon 1 (coding exon 1) of the ATRAID gene. This alteration results from a A to G substitution at nucleotide position 244, causing the arginine (R) at amino acid position 82 to be replaced by a glycine (G). 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	0.059
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	.;.;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.53	.;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.0	.;.;M
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.4	N;.;.
REVEL	Benign	0.13
Sift	Benign	0.16	T;.;.
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		0.98	D;D;.
Vest4		0.14
MutPred		0.29		Loss of helix (P = 0.028);Loss of helix (P = 0.028);.;
MVP		0.48
MPC		0.082
ClinPred		0.69	D
GERP RS		1.1
Varity_R		0.10
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1674616852; hg19: chr2-27435315;