7-26197618-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002137.4(HNRNPA2B1):c.117+4T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0314 in 1,605,510 control chromosomes in the GnomAD database, including 911 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 80 hom., cov: 32)

Exomes 𝑓: 0.031 ( 831 hom. )

Consequence

HNRNPA2B1
NM_002137.4 splice_region, intron

Scores

Splicing: ADA: 0.00002346

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.423

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 7-26197618-A-G is Benign according to our data. Variant chr7-26197618-A-G is described in ClinVar as [Benign]. Clinvar id is 261953.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-26197618-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0303 (4609/152336) while in subpopulation NFE AF= 0.0354 (2409/68030). AF 95% confidence interval is 0.0342. There are 80 homozygotes in gnomad4. There are 2176 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4609 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPA2B1	NM_002137.4 link	c.117+4T>C		splice_region_variant, intron_variant	Intron 2 of 10	ENST00000618183.5	NP_002128.1	P22626-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPA2B1	ENST00000618183.5 link	c.117+4T>C		splice_region_variant, intron_variant	Intron 2 of 10	5	NM_002137.4	ENSP00000478691.2		P22626-2A0A087WUI2

Frequencies

GnomAD3 genomes

AF:

0.0302

AC:

4604

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0278

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0272

Gnomad ASJ

AF:

0.0596

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0153

Gnomad FIN

AF:

0.0237

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0354

Gnomad OTH

AF:

0.0349

GnomAD3 exomes

AF:

0.0289

AC:

7221

AN:

250034

Hom.:

136

AF XY:

0.0290

AC XY:

3925

AN XY:

135196

show subpopulations

Gnomad AFR exome

AF:

0.0288

Gnomad AMR exome

AF:

0.0217

Gnomad ASJ exome

AF:

0.0601

Gnomad EAS exome

AF:

0.000273

Gnomad SAS exome

AF:

0.0161

Gnomad FIN exome

AF:

0.0235

Gnomad NFE exome

AF:

0.0368

Gnomad OTH exome

AF:

0.0391

GnomAD4 exome

AF:

0.0315

AC:

45729

AN:

1453174

Hom.:

831

Cov.:

AF XY:

0.0312

AC XY:

22537

AN XY:

723360

show subpopulations

Gnomad4 AFR exome

AF:

0.0299

Gnomad4 AMR exome

AF:

0.0230

Gnomad4 ASJ exome

AF:

0.0658

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0160

Gnomad4 FIN exome

AF:

0.0240

Gnomad4 NFE exome

AF:

0.0335

Gnomad4 OTH exome

AF:

0.0340

GnomAD4 genome

AF:

0.0303

AC:

4609

AN:

152336

Hom.:

Cov.:

AF XY:

0.0292

AC XY:

2176

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0279

Gnomad4 AMR

AF:

0.0272

Gnomad4 ASJ

AF:

0.0596

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.0151

Gnomad4 FIN

AF:

0.0237

Gnomad4 NFE

AF:

0.0354

Gnomad4 OTH

AF:

0.0350

Alfa

AF:

0.0344

Hom.:

Bravo

AF:

0.0307

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0371

EpiControl

AF:

0.0356

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Sep 09, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.3

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000023

dbscSNV1_RF

Benign

0.0080

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