X-101412003-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_019597.5(HNRNPH2):c.15G>A(p.Thr5=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000223 in 1,204,922 control chromosomes in the GnomAD database, including 2 homozygotes. There are 65 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., 23 hem., cov: 21)
  • Exomes 𝑓: 0.00013 (2 hom. 42 hem.)
• Consequence: HNRNPH2 NM_019597.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.60

Genes affected

HNRNPH2 (HGNC:5042): (heterogeneous nuclear ribonucleoprotein H2) This gene belongs to the 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 three repeats of quasi-RRM domains that binds to RNAs. It is very similar to the family member HNRPH1. This gene is thought to be involved in Fabray disease and X-linked agammaglobulinemia phenotype. Alternative splicing results in multiple transcript variants encoding the same protein. Read-through transcription between this locus and the ribosomal protein L36a gene has been observed. [provided by RefSeq, Jan 2011]

RPL36A-HNRNPH2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant X-101412003-G-A is Benign according to our data. Variant chrX-101412003-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2661060.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.6 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00115 (125/108392) while in subpopulation AFR AF= 0.00391 (116/29673). AF 95% confidence interval is 0.00333. There are 0 homozygotes in gnomad4. There are 23 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 23 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNRNPH2	NM_019597.5	c.15G>A	p.Thr5=	synonymous_variant	2/2	ENST00000316594.6
RPL36A-HNRNPH2	NM_001199973.2	c.*11G>A		3_prime_UTR_variant	5/5
HNRNPH2	NM_001032393.3	c.15G>A	p.Thr5=	synonymous_variant	2/2
RPL36A-HNRNPH2	NM_001199974.2	c.*11G>A		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNRNPH2	ENST00000316594.6	c.15G>A	p.Thr5=	synonymous_variant	2/2	1	NM_019597.5	P1

Frequencies

GnomAD3 genomes AF: 0.00115 AC: 125 AN: 108337 Hom.: 0 Cov.: 21 AF XY: 0.000747 AC XY: 23 AN XY: 30775

Gnomad AFR AF: 0.00392

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000596

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000382

Gnomad OTH AF: 0.000695

GnomAD3 exomes AF: 0.000334 AC: 60 AN: 179775 Hom.: 0 AF XY: 0.000388 AC XY: 25 AN XY: 64463

Gnomad AFR exome AF: 0.00351

Gnomad AMR exome AF: 0.000223

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000547

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000871

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000131 AC: 144 AN: 1096530 Hom.: 2 Cov.: 33 AF XY: 0.000116 AC XY: 42 AN XY: 362064

Gnomad4 AFR exome AF: 0.00376

Gnomad4 AMR exome AF: 0.000286

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000929

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000226

Gnomad4 OTH exome AF: 0.000239

GnomAD4 genome AF: 0.00115 AC: 125 AN: 108392 Hom.: 0 Cov.: 21 AF XY: 0.000746 AC XY: 23 AN XY: 30838

Gnomad4 AFR AF: 0.00391

Gnomad4 AMR AF: 0.000596

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000382

Gnomad4 OTH AF: 0.000686

Alfa AF: 0.000564 Hom.: 1

Bravo AF: 0.00144

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

HNRNPH2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.059
Dann	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs149708053; hg19: chrX-100666991;