rs307658

Variant names:

• chr9-33941761-T-C
• rs307658
• NM_001370062.2:c.1817A>G

Variant summary

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

The NM_001370062.2(UBAP2):​c.1817A>G​(p.Asn606Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 1,613,590 control chromosomes in the GnomAD database, including 120,041 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.40 (12457 hom., cov: 31)
  • Exomes 𝑓: 0.38 (107584 hom.)
• Consequence: UBAP2 NM_001370062.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76
• Publications: 48 publications found

Genes affected

UBAP2 (HGNC:14185): (ubiquitin associated protein 2) The protein encoded by this gene contains a UBA (ubiquitin associated) domain, which is characteristic of proteins that function in the ubiquitination pathway. This gene may show increased expression in the adrenal gland and lymphatic tissues. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011149049).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBAP2	NM_001370062.2	c.1817A>G	p.Asn606Ser	missense_variant	Exon 16 of 29	ENST00000379238.7	NP_001356991.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBAP2	ENST00000379238.7	c.1817A>G	p.Asn606Ser	missense_variant	Exon 16 of 29	5	NM_001370062.2	ENSP00000368540.2

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60486 AN: 151862 Hom.: 12430 Cov.: 31

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.367

GnomAD2 exomes AF: 0.364 AC: 91425 AN: 251426 AF XY: 0.372

Gnomad AFR exome AF: 0.479

Gnomad AMR exome AF: 0.228

Gnomad ASJ exome AF: 0.299

Gnomad EAS exome AF: 0.164

Gnomad FIN exome AF: 0.447

Gnomad NFE exome AF: 0.380

Gnomad OTH exome AF: 0.371

GnomAD4 exome AF: 0.379 AC: 554217 AN: 1461610 Hom.: 107584 Cov.: 38 AF XY: 0.383 AC XY: 278130 AN XY: 727112

African (AFR) AF: 0.480 AC: 16074 AN: 33470

American (AMR) AF: 0.238 AC: 10638 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 7762 AN: 26132

East Asian (EAS) AF: 0.225 AC: 8919 AN: 39688

South Asian (SAS) AF: 0.480 AC: 41435 AN: 86254

European-Finnish (FIN) AF: 0.445 AC: 23781 AN: 53420

Middle Eastern (MID) AF: 0.354 AC: 2043 AN: 5768

European-Non Finnish (NFE) AF: 0.379 AC: 421093 AN: 1111766

Other (OTH) AF: 0.372 AC: 22472 AN: 60388

GnomAD4 genome AF: 0.398 AC: 60561 AN: 151980 Hom.: 12457 Cov.: 31 AF XY: 0.399 AC XY: 29606 AN XY: 74268

African (AFR) AF: 0.473 AC: 19618 AN: 41448

American (AMR) AF: 0.304 AC: 4643 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 985 AN: 3466

East Asian (EAS) AF: 0.186 AC: 963 AN: 5182

South Asian (SAS) AF: 0.478 AC: 2304 AN: 4822

European-Finnish (FIN) AF: 0.432 AC: 4546 AN: 10518

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26171 AN: 67948

Other (OTH) AF: 0.367 AC: 775 AN: 2112

Alfa AF: 0.376 Hom.: 42248

Bravo AF: 0.382

TwinsUK AF: 0.375 AC: 1390

ALSPAC AF: 0.369 AC: 1423

ESP6500AA AF: 0.468 AC: 2060

ESP6500EA AF: 0.383 AC: 3291

ExAC AF: 0.374 AC: 45406

Asia WGS AF: 0.350 AC: 1220 AN: 3478

EpiCase AF: 0.370

EpiControl AF: 0.368

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.9
DANN	Benign	0.13
DEOGEN2	Benign	0.012	T;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.078	.;T
MetaRNN	Benign	0.0011	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-2.1	N;N
PhyloP100		1.8
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.50	N;N
REVEL	Benign	0.11
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.020	B;B
Vest4		0.025
MPC		0.055
ClinPred		0.0040	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.022
gMVP		0.088
Mutation Taster		=98/2	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: rs307658; hg19: chr9-33941759; COSMIC: COSV62545734; COSMIC: COSV62545734;