Variant rs34317198 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002137.4(HNRNPA2B1):c.519A>G(p.Arg173=) 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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 261954.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-26196615-T-C is described in Lovd as [Likely_benign].

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNRNPA2B1	NM_002137.4 linkuse as main transcript	c.519A>G	p.Arg173=	synonymous_variant	5/11	ENST00000618183.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNRNPA2B1	ENST00000618183.5 linkuse as main transcript	c.519A>G	p.Arg173=	synonymous_variant	5/11	5	NM_002137.4	A1	P22626-2

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

GnomAD3 exomes

AF:

0.0121

AC:

3040

AN:

251382

Hom.:

223

AF XY:

0.00874

AC XY:

1188

AN XY:

135868

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 SAS exome

AF:

0.000392

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

Gnomad4 AFR exome

AF:

0.162

Gnomad4 AMR exome

AF:

0.00993

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000281

Gnomad4 OTH exome

AF:

0.0110

GnomAD4 genome

AF:

0.0451

AC:

6861

AN:

152286

Hom.:

550

Cov.:

AF XY:

0.0442

AC XY:

3290

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.156

Gnomad4 AMR

AF:

0.0163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000676

Gnomad4 OTH

AF:

0.0307

Alfa

AF:

0.0212

Hom.:

118

Bravo

AF:

0.0511

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.91

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over