rs770859949

Variant names:

• chr19-55529866-C-G
• rs770859949
• NM_001370096.2:c.914G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-55529866-C-G
• chr19-55529866-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001370096.2(SBK2):​c.914G>C​(p.Arg305Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,172 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R305Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SBK2 NM_001370096.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200

Genes affected

SBK2 (HGNC:34416): (SH3 domain binding kinase family member 2) Predicted to enable MAP kinase kinase activity. Predicted to be involved in MAPK cascade and protein phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBK2	NM_001370096.2	c.914G>C	p.Arg305Pro	missense_variant	Exon 4 of 4	ENST00000413299.6	NP_001357025.1
SBK2	XM_011527227.3	c.*473G>C		3_prime_UTR_variant	Exon 4 of 4		XP_011525529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBK2	ENST00000413299.6	c.914G>C	p.Arg305Pro	missense_variant	Exon 4 of 4	5	NM_001370096.2	ENSP00000389015.2
SBK2	ENST00000344158.4	c.914G>C	p.Arg305Pro	missense_variant	Exon 3 of 3	2		ENSP00000345044.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000466 AC: 1 AN: 214778 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 119882

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000111

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 6.91e-7 AC: 1 AN: 1446172 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 719178

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000389

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.061	T;T
Eigen	Benign	-0.076
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.26	T;.
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Uncertain	0.29
Sift	Benign	0.15	T;T
Sift4G	Benign	0.15	T;T
Polyphen		1.0	D;D
Vest4		0.39
MutPred		0.71		Loss of MoRF binding (P = 0.0237);Loss of MoRF binding (P = 0.0237);
MVP		0.64
MPC		1.4
ClinPred		0.75	D
GERP RS		1.7
Varity_R		0.65
gMVP		0.76

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

LitVar

Other links and lift over

dbSNP: rs770859949; hg19: chr19-56041233;