10-62257024-C-T

Variant names:

• chr10-62257024-C-T
• rs3852407
• NM_145307.4:c.257+5601G>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.257+5601G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 151,746 control chromosomes in the GnomAD database, including 40,846 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 0.73 (40846 hom., cov: 31)
• Consequence: RTKN2 NM_145307.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.717
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTKN2	NM_145307.4	c.257+5601G>A		intron_variant	Intron 2 of 11	ENST00000373789.8	NP_660350.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTKN2	ENST00000373789.8	c.257+5601G>A		intron_variant	Intron 2 of 11	1	NM_145307.4	ENSP00000362894.3
RTKN2	ENST00000395260.3	c.257+5601G>A		intron_variant	Intron 2 of 4	1		ENSP00000378678.3

Frequencies

GnomAD3 genomes AF: 0.732 AC: 110995 AN: 151626 Hom.: 40832 Cov.: 31

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.897

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.730

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

GnomAD4 genome AF: 0.732 AC: 111055 AN: 151746 Hom.: 40846 Cov.: 31 AF XY: 0.734 AC XY: 54399 AN XY: 74136

African (AFR) AF: 0.660 AC: 27360 AN: 41426

American (AMR) AF: 0.773 AC: 11797 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2547 AN: 3378

East Asian (EAS) AF: 0.896 AC: 4636 AN: 5172

South Asian (SAS) AF: 0.599 AC: 2880 AN: 4808

European-Finnish (FIN) AF: 0.815 AC: 8598 AN: 10546

Middle Eastern (MID) AF: 0.712 AC: 208 AN: 292

European-Non Finnish (NFE) AF: 0.749 AC: 50840 AN: 67842

Other (OTH) AF: 0.727 AC: 1533 AN: 2108

Alfa AF: 0.543 Hom.: 866

Bravo AF: 0.730

Asia WGS AF: 0.746 AC: 2591 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.63
PhyloP100		-0.72
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: rs3852407; hg19: chr10-64016783;