2-127489841-C-T

Variant names:

• chr2-127489841-C-T
• rs1469391150
• NM_017969.3:c.2150G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_017969.3(IWS1):​c.2150G>A​(p.Arg717Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000557 in 1,435,786 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: IWS1 NM_017969.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.41
• Publications: 0 publications found

Genes affected

IWS1 (HGNC:25467): (interacts with SUPT6H, CTD assembly factor 1) Involved in regulation of histone modification; regulation of mRNA export from nucleus; and regulation of mRNA processing. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000231731 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.1706444).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017969.3. 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
	IWS1	NM_017969.3	MANE Select	c.2150G>A	p.Arg717Lys	missense	Exon 11 of 14	NP_060439.2	Q96ST2-1
	IWS1	NM_001410923.1		c.2150G>A	p.Arg717Lys	missense	Exon 11 of 15	NP_001397852.1	A0A1B0GW95

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IWS1	ENST00000295321.9	TSL:1 MANE Select	c.2150G>A	p.Arg717Lys	missense	Exon 11 of 14	ENSP00000295321.4	Q96ST2-1
	IWS1	ENST00000637187.2	TSL:5	c.2150G>A	p.Arg717Lys	missense	Exon 11 of 15	ENSP00000490836.2	A0A1B0GW95
	IWS1	ENST00000866713.1		c.2147G>A	p.Arg716Lys	missense	Exon 11 of 14	ENSP00000536772.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000557 AC: 8 AN: 1435786 Hom.: 0 Cov.: 27 AF XY: 0.00000559 AC XY: 4 AN XY: 716162

African (AFR) AF: 0.00 AC: 0 AN: 32974

American (AMR) AF: 0.00 AC: 0 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25978

East Asian (EAS) AF: 0.00 AC: 0 AN: 39558

South Asian (SAS) AF: 0.00 AC: 0 AN: 85722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5720

European-Non Finnish (NFE) AF: 0.00000643 AC: 7 AN: 1088270

Other (OTH) AF: 0.00 AC: 0 AN: 59520

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.21
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Uncertain	23
DANN	Benign	0.96
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.24
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		5.4
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.053
Sift	Benign	0.18	T
Sift4G	Benign	0.24	T
Polyphen		0.025	B
Vest4		0.12
MVP		0.54
MPC		1.6
ClinPred		0.67	D
GERP RS		4.1
Varity_R		0.21
gMVP		0.78
Mutation Taster		=84/16	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: rs1469391150; hg19: chr2-128247417;