chr11-67432235-C-G

Variant names:

• chr11-67432235-C-G
• rs1638588
• NM_003952.3:c.458-365C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003952.3(RPS6KB2):​c.458-365C>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPS6KB2 NM_003952.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321
• Publications: 18 publications found

Genes affected

RPS6KB2 (HGNC:10437): (ribosomal protein S6 kinase B2) This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains a kinase catalytic domain and phosphorylates the S6 ribosomal protein and eukaryotic translation initiation factor 4B (eIF4B). Phosphorylation of S6 leads to an increase in protein synthesis and cell proliferation. [provided by RefSeq, Jan 2015]

RPS6KB2-AS1 (HGNC:53744): (RPS6KB2 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003952.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KB2	NM_003952.3	MANE Select	c.458-365C>G		intron	N/A	NP_003943.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KB2	ENST00000312629.10	TSL:1 MANE Select	c.458-365C>G		intron	N/A	ENSP00000308413.5
	RPS6KB2	ENST00000525088.5	TSL:2	n.3445C>G		non_coding_transcript_exon	Exon 2 of 8
	RPS6KB2	ENST00000420069.3	TSL:3	c.-85-502C>G		intron	N/A	ENSP00000410175.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 354396 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 196812

African (AFR) AF: 0.00 AC: 0 AN: 10528

American (AMR) AF: 0.00 AC: 0 AN: 27932

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12974

East Asian (EAS) AF: 0.00 AC: 0 AN: 13566

South Asian (SAS) AF: 0.00 AC: 0 AN: 59340

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16122

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3114

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 192732

Other (OTH) AF: 0.00 AC: 0 AN: 18088

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.13
DANN	Benign	0.16
PhyloP100		-0.32

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: rs1638588; hg19: chr11-67199706;