Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002137.4(HNRNPA2B1):c.519A>G(p.Arg173Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00855 in 1,614,040 control chromosomes in the GnomAD database, including 1,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 550 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 467 hom. )

Consequence

HNRNPA2B1
NM_002137.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.960

Publications

3 publications found

Variant links:

Genes affected

HNRNPA2B1 (HGNC:5033): (heterogeneous nuclear ribonucleoprotein A2/B1) This gene belongs to the A/B subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has two repeats of quasi-RRM domains that bind to RNAs. This gene has been described to generate two alternatively spliced transcript variants which encode different isoforms. [provided by RefSeq, Jul 2008]

HNRNPA2B1 Gene-Disease associations (from GenCC):

inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
oculopharyngeal muscular dystrophy 2
Inheritance: AD Classification: STRONG Submitted by: G2P
amyotrophic lateral sclerosis
Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Genomics England PanelApp, ClinGen
inclusion body myopathy with Paget disease of bone and frontotemporal dementia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

HNRNPA2B1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 7-26196615-T-C is Benign according to our data. Variant chr7-26196615-T-C is described in ClinVar as Benign. ClinVar VariationId is 261954.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.96 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002137.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
HNRNPA2B1	NM_002137.4	MANE Select	c.519A>G	p.Arg173Arg	synonymous	Exon 5 of 11	NP_002128.1
HNRNPA2B1	NM_001438568.1		c.555A>G	p.Arg185Arg	synonymous	Exon 6 of 12	NP_001425497.1
HNRNPA2B1	NM_001438569.1		c.555A>G	p.Arg185Arg	synonymous	Exon 6 of 12	NP_001425498.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
HNRNPA2B1	ENST00000618183.5	TSL:5 MANE Select	c.519A>G	p.Arg173Arg	synonymous	Exon 5 of 11	ENSP00000478691.2
HNRNPA2B1	ENST00000354667.8	TSL:1	c.555A>G	p.Arg185Arg	synonymous	Exon 6 of 12	ENSP00000346694.4
HNRNPA2B1	ENST00000356674.8	TSL:1	c.555A>G	p.Arg185Arg	synonymous	Exon 6 of 11	ENSP00000349101.8

Frequencies

GnomAD3 genomes

AF:

0.0450

AC:

6844

AN:

152168

Hom.:

548

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0163

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.0311

GnomAD2 exomes

AF:

0.0121

AC:

3040

AN:

251382

AF XY:

0.00874

show subpopulations

Gnomad AFR exome

AF:

0.162

Gnomad AMR exome

AF:

0.00870

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000528

Gnomad OTH exome

AF:

0.00701

GnomAD4 exome

AF:

0.00475

AC:

6942

AN:

1461754

Hom.:

467

Cov.:

AF XY:

0.00414

AC XY:

3012

AN XY:

727188

show subpopulations

African (AFR)

AF:

0.162

AC:

5415

AN:

33444

American (AMR)

AF:

0.00993

AC:

444

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000765

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39684

South Asian (SAS)

AF:

0.000267

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.0140

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000281

AC:

312

AN:

1111950

Other (OTH)

AF:

0.0110

AC:

664

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

318

636

955

1273

1591

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

336

504

672

840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0451

AC:

6861

AN:

152286

Hom.:

550

Cov.:

AF XY:

0.0442

AC XY:

3290

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.156

AC:

6498

AN:

41530

American (AMR)

AF:

0.0163

AC:

249

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000676

AC:

AN:

68022

Other (OTH)

AF:

0.0307

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

293

586

880

1173

1466

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0210

Hom.:

176

Bravo

AF:

0.0511

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.000533

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

0.96

Mutation Taster

=84/16

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs34317198

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over