chr1-37567000-C-T

Variant names:

• chr1-37567000-C-T
• rs758821126
• NM_013285.3:c.2051G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_013285.3(GNL2):​c.2051G>A​(p.Arg684Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000106 in 1,610,414 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: GNL2 NM_013285.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.96
• Publications: 2 publications found

Genes affected

GNL2 (HGNC:29925): (G protein nucleolar 2) Enables RNA binding activity. Predicted to be involved in ribosome biogenesis. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

DNALI1 (HGNC:14353): (dynein axonemal light intermediate chain 1) This gene is the human homolog of the Chlamydomonas inner dynein arm gene, p28. The precise function of this gene is not known, however, it is a potential candidate for immotile cilia syndrome (ICS). Ultrastructural defects of the inner dynein arms are seen in patients with ICS. Immotile mutant strains of Chlamydomonas, a biflagellated algae, exhibit similar defects. [provided by RefSeq, Jul 2008]

DNALI1 Gene-Disease associations (from GenCC):

• spermatogenic failure 83

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28959107).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013285.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNL2	NM_013285.3	MANE Select	c.2051G>A	p.Arg684Gln	missense	Exon 16 of 16	NP_037417.1	Q5T0F3
	GNL2	NM_001323623.2		c.2255G>A	p.Arg752Gln	missense	Exon 17 of 17	NP_001310552.1
	GNL2	NM_001323624.2		c.1502G>A	p.Arg501Gln	missense	Exon 15 of 15	NP_001310553.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNL2	ENST00000373062.8	TSL:1 MANE Select	c.2051G>A	p.Arg684Gln	missense	Exon 16 of 16	ENSP00000362153.3	Q13823
	GNL2	ENST00000852774.1		c.2078G>A	p.Arg693Gln	missense	Exon 16 of 16	ENSP00000522833.1
	GNL2	ENST00000965152.1		c.2048G>A	p.Arg683Gln	missense	Exon 16 of 16	ENSP00000635211.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151892 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 247882 AF XY: 0.0000150

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000888

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000891 AC: 13 AN: 1458522 Hom.: 0 Cov.: 31 AF XY: 0.00000827 AC XY: 6 AN XY: 725172

African (AFR) AF: 0.00 AC: 0 AN: 33342

American (AMR) AF: 0.0000227 AC: 1 AN: 44086

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26044

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39686

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111080

Other (OTH) AF: 0.0000166 AC: 1 AN: 60302

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151892 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74156

African (AFR) AF: 0.0000242 AC: 1 AN: 41304

American (AMR) AF: 0.000131 AC: 2 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68014

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000982

ExAC AF: 0.00000824 AC: 1

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.060	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		6.0
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.099
Sift	Benign	0.19	T
Sift4G	Benign	0.33	T
Polyphen		1.0	D
Vest4		0.37
MutPred		0.24		Gain of helix (P = 0.132)
MVP		0.31
MPC		0.50
ClinPred		0.92	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.19
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs758821126; hg19: chr1-38032601;