Genetic Variant HNRNPA1L2:p.Gly211Ser (chr13-52643123-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001389320.1(HNRNPA1L2):c.631G>A(p.Gly211Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,597,978 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 2 hom. )

Consequence

HNRNPA1L2
NM_001389320.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.74

Variant links:

Genes affected

HNRNPA1L2 (HGNC:27067): (heterogeneous nuclear ribonucleoprotein A1 like 2) Predicted to enable RNA binding activity. Predicted to be involved in RNA splicing; mRNA processing; and mRNA transport. Predicted to be located in cytoplasm. Predicted to be part of spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

HNRNPA1L2 links:

ENSG00000273784 (HGNC:):

ENSG00000273784 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019142807).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPA1L2	NM_001389320.1 link	c.631G>A	p.Gly211Ser	missense_variant	Exon 1 of 1	ENST00000357495.5	NP_001376249.1
HNRNPA1L2	NM_001011724.3 link	c.631G>A	p.Gly211Ser	missense_variant	Exon 7 of 7		NP_001011724.1	Q32P51A0A024QZ98
HNRNPA1L2	NM_001011725.3 link	c.631G>A	p.Gly211Ser	missense_variant	Exon 6 of 6		NP_001011725.1	Q32P51A0A024QZ98

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPA1L2	ENST00000357495.5 link	c.631G>A	p.Gly211Ser	missense_variant	Exon 1 of 1	6	NM_001389320.1	ENSP00000350090.2		Q32P51
ENSG00000273784	ENST00000683187.1 link	n.1508G>A		non_coding_transcript_exon_variant	Exon 6 of 6

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000212

AC:

AN:

236094

Hom.:

AF XY:

0.000271

AC XY:

AN XY:

128960

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000998

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000151

AC:

219

AN:

1445680

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

137

AN XY:

719596

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00120

Gnomad4 FIN exome

AF:

0.0000255

Gnomad4 NFE exome

AF:

0.0000908

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000118

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000239

AC:

ExAC

AF:

0.000217

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 03, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.631G>A (p.G211S) alteration is located in exon 7 (coding exon 1) of the HNRNPA1L2 gene. This alteration results from a G to A substitution at nucleotide position 631, causing the glycine (G) at amino acid position 211 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.023

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.80

M_CAP

Benign

0.015

MetaRNN

Benign

0.019

MetaSVM

Uncertain

-0.12

MutationAssessor

Uncertain

2.1

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.18

Sift

Benign

0.17

Sift4G

Uncertain

0.049

Polyphen

0.0020

Vest4

0.16

MVP

0.39

ClinPred

0.053

GERP RS

0.35

Varity_R

0.042

gMVP

0.64

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