2-41953045-T-C

Variant names:

• chr2-41953045-T-C
• rs200161608
• ENST00000378711.2:n.341A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000378711.2(LINC02898):​n.341A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000983 in 1,551,032 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00095 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00099 (1 hom.)
• Consequence: LINC02898 ENST00000378711.2 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.140
• Publications: 1 publications found

Genes affected

LINC02898 (HGNC:42966): (long intergenic non-protein coding RNA 2898)

ENSG00000299946 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0078119636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINC02898	NR_161189.1	n.344A>G		non_coding_transcript_exon_variant	Exon 2 of 4
LOC124905996	XR_007086296.1	n.613T>C		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINC02898	ENST00000378711.2	n.341A>G		non_coding_transcript_exon_variant	Exon 2 of 4	2
LINC02898	ENST00000403980.1	n.515A>G		non_coding_transcript_exon_variant	Exon 2 of 2	3
LINC02898	ENST00000615044.1	n.251A>G		non_coding_transcript_exon_variant	Exon 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.000953 AC: 145 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00162

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000686 AC: 104 AN: 151634 AF XY: 0.000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000162

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000293

Gnomad NFE exome AF: 0.00117

Gnomad OTH exome AF: 0.000899

GnomAD4 exome AF: 0.000987 AC: 1381 AN: 1398718 Hom.: 1 Cov.: 31 AF XY: 0.00104 AC XY: 718 AN XY: 689844

African (AFR) AF: 0.000127 AC: 4 AN: 31580

American (AMR) AF: 0.000364 AC: 13 AN: 35710

Ashkenazi Jewish (ASJ) AF: 0.0000397 AC: 1 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35718

South Asian (SAS) AF: 0.00110 AC: 87 AN: 79234

European-Finnish (FIN) AF: 0.000351 AC: 17 AN: 48478

Middle Eastern (MID) AF: 0.000701 AC: 4 AN: 5704

European-Non Finnish (NFE) AF: 0.00111 AC: 1201 AN: 1078926

Other (OTH) AF: 0.000928 AC: 54 AN: 58186

GnomAD4 genome AF: 0.000945 AC: 144 AN: 152314 Hom.: 0 Cov.: 32 AF XY: 0.000765 AC XY: 57 AN XY: 74490

African (AFR) AF: 0.000168 AC: 7 AN: 41560

American (AMR) AF: 0.00105 AC: 16 AN: 15310

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00162 AC: 110 AN: 68024

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00116 Hom.: 0

Bravo AF: 0.000967

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000778 AC: 3

ExAC AF: 0.000659 AC: 15

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.251A>G (p.Q84R) alteration is located in exon 2 (coding exon 1) of the C2orf91 gene. This alteration results from a A to G substitution at nucleotide position 251, causing the glutamine (Q) at amino acid position 84 to be replaced by an arginine (R). 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	0.15
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.2
DANN	Benign	0.82
DEOGEN2	Benign	0.054	T;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.37	T;T
M_CAP	Benign	0.00096	T
MetaRNN	Benign	0.0078	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.
PhyloP100		0.14
MVP		0.040
ClinPred		0.099	T
GERP RS		-0.55
Varity_R		0.49
gMVP		0.014
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs200161608; hg19: chr2-42180185;