10-62214496-G-T

Variant names:

• chr10-62214496-G-T
• rs10733769
• NM_145307.4:c.1020+2622C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145307.4(RTKN2):​c.1020+2622C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 151,978 control chromosomes in the GnomAD database, including 25,468 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.57 (25468 hom., cov: 32)
• Consequence: RTKN2 NM_145307.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.810
• Publications: 7 publications found

Genes affected

RTKN2 (HGNC:19364): (rhotekin 2) Involved in negative regulation of intrinsic apoptotic signaling pathway; positive regulation of NF-kappaB transcription factor activity; and positive regulation of NIK/NF-kappaB signaling. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTKN2	NM_145307.4	c.1020+2622C>A		intron_variant	Intron 9 of 11	ENST00000373789.8	NP_660350.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTKN2	ENST00000373789.8	c.1020+2622C>A		intron_variant	Intron 9 of 11	1	NM_145307.4	ENSP00000362894.3
RTKN2	ENST00000315289.6	c.426+533C>A		intron_variant	Intron 5 of 8	2		ENSP00000325379.2

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87158 AN: 151860 Hom.: 25471 Cov.: 32

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.582

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.574 AC: 87181 AN: 151978 Hom.: 25468 Cov.: 32 AF XY: 0.577 AC XY: 42835 AN XY: 74282

African (AFR) AF: 0.482 AC: 19971 AN: 41446

American (AMR) AF: 0.642 AC: 9790 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2084 AN: 3468

East Asian (EAS) AF: 0.899 AC: 4663 AN: 5186

South Asian (SAS) AF: 0.500 AC: 2413 AN: 4826

European-Finnish (FIN) AF: 0.638 AC: 6740 AN: 10566

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39700 AN: 67918

Other (OTH) AF: 0.581 AC: 1224 AN: 2108

Alfa AF: 0.584 Hom.: 76787

Bravo AF: 0.579

Asia WGS AF: 0.682 AC: 2367 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.1
DANN	Benign	0.65
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism (auto)

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: rs10733769; hg19: chr10-63974255;