2-113007907-A-G

Variant names:

• chr2-113007907-A-G
• NM_014440.3:c.340A>G

Variant summary

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

The NM_014440.3(IL36A):​c.340A>G​(p.Arg114Gly) variant causes a missense 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. 14/21 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)
• Consequence: IL36A NM_014440.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.562

Genes affected

IL36A (HGNC:15562): (interleukin 36 alpha) The protein encoded by this gene is a cytokine that can activate NF-kappa-B and MAPK signaling pathways to generate an inflammatory response. The encoded protein functions primarily in skin and demonstrates increased expression in psoriasis. In addition, decreased expression of this gene has been linked to a poor prognosis in both hepatocellular carcinoma and colorectal cancer patients. [provided by RefSeq, Nov 2015]

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=0.15024164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL36A	NM_014440.3	c.340A>G	p.Arg114Gly	missense_variant	Exon 4 of 4	ENST00000259211.7	NP_055255.1
IL36A	XM_005263639.3	c.340A>G	p.Arg114Gly	missense_variant	Exon 4 of 5		XP_005263696.1
IL36A	XM_011510965.2	c.340A>G	p.Arg114Gly	missense_variant	Exon 4 of 5		XP_011509267.1
IL36A	XM_017003806.2	c.340A>G	p.Arg114Gly	missense_variant	Exon 4 of 5		XP_016859295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL36A	ENST00000259211.7	c.340A>G	p.Arg114Gly	missense_variant	Exon 4 of 4	1	NM_014440.3	ENSP00000259211.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.340A>G (p.R114G) alteration is located in exon 4 (coding exon 4) of the IL36A gene. This alteration results from a A to G substitution at nucleotide position 340, causing the arginine (R) at amino acid position 114 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	0.18
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.039
Sift	Benign	0.20	T
Sift4G	Benign	0.20	T
Polyphen		0.91	P
Vest4		0.097
MutPred		0.36		Loss of solvent accessibility (P = 0.0159);
MVP		0.20
MPC		0.088
ClinPred		0.52	D
GERP RS		2.3
Varity_R		0.17
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
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: chr2-113765484;