rs756001347

Variant names:

• chr1-166920759-G-A
• rs756001347
• NM_199351.3:c.1832C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-166920759-G-A
• chr1-166920759-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_199351.3(ILDR2):​c.1832C>T​(p.Pro611Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000671 in 1,490,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000067 (0 hom.)
• Consequence: ILDR2 NM_199351.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.31

Genes affected

ILDR2 (HGNC:18131): (immunoglobulin like domain containing receptor 2) Predicted to act upstream of or within several processes, including homeostasis of number of cells within a tissue; insulin secretion; and response to glucose. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13251087).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ILDR2	NM_199351.3	c.1832C>T	p.Pro611Leu	missense_variant	Exon 9 of 10	ENST00000271417.8	NP_955383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ILDR2	ENST00000271417.8	c.1832C>T	p.Pro611Leu	missense_variant	Exon 9 of 10	1	NM_199351.3	ENSP00000271417.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 115950 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000673 AC: 9 AN: 1337946 Hom.: 0 Cov.: 32 AF XY: 0.00000304 AC XY: 2 AN XY: 658192

African (AFR) AF: 0.00 AC: 0 AN: 27074

American (AMR) AF: 0.00 AC: 0 AN: 26772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22068

East Asian (EAS) AF: 0.00 AC: 0 AN: 31440

South Asian (SAS) AF: 0.00 AC: 0 AN: 71400

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5402

European-Non Finnish (NFE) AF: 0.00000855 AC: 9 AN: 1052062

Other (OTH) AF: 0.00 AC: 0 AN: 54846

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74338

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000132 Hom.: 0

ExAC AF: 0.00000855 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1832C>T (p.P611L) alteration is located in exon 9 (coding exon 9) of the ILDR2 gene. This alteration results from a C to T substitution at nucleotide position 1832, causing the proline (P) at amino acid position 611 to be replaced by a leucine (L). 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	0.087
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.092	T;T;T;.;T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.85	T;T;T;T;T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;.;.;.;.
PhyloP100		4.3
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.0	N;N;N;N;N
REVEL	Benign	0.10
Sift	Benign	0.10	T;T;T;T;T
Sift4G	Benign	0.15	T;T;T;T;T
Polyphen		0.0	B;.;.;.;.
Vest4		0.092
MutPred		0.23		Gain of sheet (P = 0.0036);.;.;.;.;
MVP		0.52
MPC		1.2
ClinPred		0.30	T
GERP RS		2.5
Varity_R		0.12
gMVP		0.13
Mutation Taster		=96/4	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

Publications

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Other links and lift over

dbSNP: rs756001347; hg19: chr1-166889996;