rs73936310

Variant names:

• chr19-55661159-C-T
• rs73936310
• NM_007279.3:c.456C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_007279.3(U2AF2):​c.456C>T​(p.Tyr152Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00383 in 1,610,678 control chromosomes in the GnomAD database, including 216 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (102 hom., cov: 31)
  • Exomes 𝑓: 0.0022 (114 hom.)
• Consequence: U2AF2 NM_007279.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0550
• Publications: 1 publications found

Genes affected

U2AF2 (HGNC:23156): (U2 small nuclear RNA auxiliary factor 2) U2 auxiliary factor (U2AF), comprised of a large and a small subunit, is a non-snRNP protein required for the binding of U2 snRNP to the pre-mRNA branch site. This gene encodes the U2AF large subunit which contains a sequence-specific RNA-binding region with 3 RNA recognition motifs and an Arg/Ser-rich domain necessary for splicing. The large subunit binds to the polypyrimidine tract of introns early during spliceosome assembly. Multiple transcript variants have been detected for this gene, but the full-length natures of only two have been determined to date. [provided by RefSeq, Jul 2008]

U2AF2 Gene-Disease associations (from GenCC):

• developmental delay, dysmorphic facies, and brain anomalies

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 19-55661159-C-T is Benign according to our data. Variant chr19-55661159-C-T is described in ClinVar as Benign. ClinVar VariationId is 789674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.055 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0658 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007279.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	U2AF2	NM_007279.3	MANE Select	c.456C>T	p.Tyr152Tyr	synonymous	Exon 5 of 12	NP_009210.1	P26368-1
	U2AF2	NM_001012478.2		c.456C>T	p.Tyr152Tyr	synonymous	Exon 5 of 12	NP_001012496.1	P26368-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	U2AF2	ENST00000308924.9	TSL:1 MANE Select	c.456C>T	p.Tyr152Tyr	synonymous	Exon 5 of 12	ENSP00000307863.3	P26368-1
	U2AF2	ENST00000450554.6	TSL:1	c.456C>T	p.Tyr152Tyr	synonymous	Exon 5 of 12	ENSP00000388475.1	P26368-2
	U2AF2	ENST00000890136.1		c.492C>T	p.Tyr164Tyr	synonymous	Exon 5 of 12	ENSP00000560195.1

Frequencies

GnomAD3 genomes AF: 0.0193 AC: 2928 AN: 152004 Hom.: 101 Cov.: 31

Gnomad AFR AF: 0.0677

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00557

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00520 AC: 1295 AN: 248930 AF XY: 0.00357

Gnomad AFR exome AF: 0.0681

Gnomad AMR exome AF: 0.00382

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000275

Gnomad OTH exome AF: 0.00382

GnomAD4 exome AF: 0.00221 AC: 3223 AN: 1458556 Hom.: 114 Cov.: 31 AF XY: 0.00190 AC XY: 1381 AN XY: 725332

African (AFR) AF: 0.0723 AC: 2414 AN: 33406

American (AMR) AF: 0.00440 AC: 196 AN: 44536

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26050

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39544

South Asian (SAS) AF: 0.000477 AC: 41 AN: 85990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52718

Middle Eastern (MID) AF: 0.00930 AC: 53 AN: 5698

European-Non Finnish (NFE) AF: 0.000167 AC: 185 AN: 1110382

Other (OTH) AF: 0.00548 AC: 330 AN: 60232

GnomAD4 genome AF: 0.0193 AC: 2941 AN: 152122 Hom.: 102 Cov.: 31 AF XY: 0.0183 AC XY: 1358 AN XY: 74368

African (AFR) AF: 0.0678 AC: 2812 AN: 41448

American (AMR) AF: 0.00543 AC: 83 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 67972

Other (OTH) AF: 0.0114 AC: 24 AN: 2114

Alfa AF: 0.0104 Hom.: 26

Bravo AF: 0.0220

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.1
DANN	Benign	0.75
PhyloP100		-0.055
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs73936310; hg19: chr19-56172525;