chr17-42022472-G-A

Variant names:

• chr17-42022472-G-A
• rs2052478982
• NM_017595.6:c.168G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001144928.2(NKIRAS2):​c.168G>A​(p.Gln56Gln) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NKIRAS2 NM_001144928.2 splice_region, synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.54
• Publications: 0 publications found

Genes affected

NKIRAS2 (HGNC:17898): (NFKB inhibitor interacting Ras like 2) Predicted to enable GTPase activating protein binding activity. Predicted to be involved in I-kappaB kinase/NF-kappaB signaling. Predicted to act upstream of or within several processes, including Ral protein signal transduction; regulation of signal transduction; and surfactant homeostasis. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 17-42022472-G-A is Benign according to our data. Variant chr17-42022472-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3200301.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.54 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144928.2. 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
	NKIRAS2	NM_017595.6	MANE Select	c.168G>A	p.Gln56Gln	synonymous	Exon 3 of 4	NP_060065.2
	NKIRAS2	NM_001001349.2		c.168G>A	p.Gln56Gln	synonymous	Exon 3 of 4	NP_001001349.1	Q9NYR9-1
	NKIRAS2	NM_001144927.2		c.168G>A	p.Gln56Gln	synonymous	Exon 3 of 4	NP_001138399.1	Q9NYR9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKIRAS2	ENST00000393885.9	TSL:1 MANE Select	c.168G>A	p.Gln56Gln	synonymous	Exon 3 of 4	ENSP00000377463.3	Q9NYR9-1
	NKIRAS2	ENST00000307641.9	TSL:1	c.168G>A	p.Gln56Gln	synonymous	Exon 3 of 4	ENSP00000303580.5	Q9NYR9-1
	NKIRAS2	ENST00000393879.3	TSL:1	n.2057G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461214 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726774

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.0000224 AC: 1 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111448

Other (OTH) AF: 0.0000166 AC: 1 AN: 60366

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	14
DANN	Benign	0.89
PhyloP100		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2052478982; hg19: chr17-40174490;