Variant rs141885504 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_002137.4(HNRNPA2B1):c.744C>T(p.Pro248=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000351 in 1,611,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 0 hom. )

Consequence

HNRNPA2B1
NM_002137.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.06

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.058010817).

BP6

Variant 7-26193672-G-A is Benign according to our data. Variant chr7-26193672-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 474503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-26193672-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=2.06 with no splicing effect.

BS2

High AC in GnomAd4 at 47 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNRNPA2B1	NM_002137.4 linkuse as main transcript	c.744C>T	p.Pro248=	synonymous_variant	8/11	ENST00000618183.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNRNPA2B1	ENST00000618183.5 linkuse as main transcript	c.744C>T	p.Pro248=	synonymous_variant	8/11	5	NM_002137.4	A1	P22626-2

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

151944

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000471

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000358

AC:

AN:

248678

Hom.:

AF XY:

0.000372

AC XY:

AN XY:

134536

show subpopulations

Gnomad AFR exome

AF:

0.000248

Gnomad AMR exome

AF:

0.0000594

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000166

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000555

Gnomad NFE exome

AF:

0.000593

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000355

AC:

518

AN:

1459282

Hom.:

Cov.:

AF XY:

0.000339

AC XY:

246

AN XY:

726032

show subpopulations

Gnomad4 AFR exome

AF:

0.000210

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000506

Gnomad4 NFE exome

AF:

0.000406

Gnomad4 OTH exome

AF:

0.000332

GnomAD4 genome

AF:

0.000309

AC:

AN:

151944

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

AN XY:

74186

show subpopulations

Gnomad4 AFR

AF:

0.000242

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000284

Gnomad4 NFE

AF:

0.000471

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000445

Hom.:

Bravo

AF:

0.000351

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000371

AC:

EpiCase

AF:

0.000437

EpiControl

AF:

0.000298

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 08, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.32

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.49

MetaRNN

Benign

0.058

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D

Sift4G

Uncertain

0.039

Vest4

0.21

MVP

0.64

ClinPred

0.086

GERP RS

3.7

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

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

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