chr2-183132715-A-G

Variant names:

• chr2-183132715-A-G
• rs10497621
• NM_138285.5:c.340-851A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138285.5(NUP35):​c.340-851A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.054 in 152,320 control chromosomes in the GnomAD database, including 284 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.054 (284 hom., cov: 32)
• Consequence: NUP35 NM_138285.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 4 publications found

Genes affected

NUP35 (HGNC:29797): (nucleoporin 35) This gene encodes a member of the nucleoporin family. The encoded protein contains two membrane binding regions, is localized to the nuclear rim, and is part of the nuclear pore complex. All molecules entering or leaving the nucleus either diffuse through or are actively transported by the nuclear pore complex. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene have been defined on chromosomes 7 and 10. [provided by RefSeq, Dec 2013]

ENSG00000224643 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0739 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138285.5. 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
	NUP35	NM_138285.5	MANE Select	c.340-851A>G		intron	N/A	NP_612142.2
	NUP35	NM_001287584.2		c.289-851A>G		intron	N/A	NP_001274513.1	Q8NFH5-2
	NUP35	NM_001287585.2		c.-15-851A>G		intron	N/A	NP_001274514.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP35	ENST00000295119.9	TSL:1 MANE Select	c.340-851A>G		intron	N/A	ENSP00000295119.4	Q8NFH5-1
	NUP35	ENST00000966637.1		c.340-851A>G		intron	N/A	ENSP00000636696.1
	NUP35	ENST00000409798.5	TSL:2	c.289-851A>G		intron	N/A	ENSP00000387305.1	Q8NFH5-2

Frequencies

GnomAD3 genomes AF: 0.0541 AC: 8235 AN: 152202 Hom.: 284 Cov.: 32

Gnomad AFR AF: 0.0135

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0644

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0360

Gnomad FIN AF: 0.0568

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0756

Gnomad OTH AF: 0.0611

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0540 AC: 8232 AN: 152320 Hom.: 284 Cov.: 32 AF XY: 0.0540 AC XY: 4023 AN XY: 74480

African (AFR) AF: 0.0134 AC: 558 AN: 41578

American (AMR) AF: 0.0643 AC: 983 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 542 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5192

South Asian (SAS) AF: 0.0360 AC: 174 AN: 4832

European-Finnish (FIN) AF: 0.0568 AC: 602 AN: 10606

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0756 AC: 5143 AN: 68026

Other (OTH) AF: 0.0605 AC: 128 AN: 2116

Alfa AF: 0.0726 Hom.: 365

Bravo AF: 0.0533

Asia WGS AF: 0.0120 AC: 44 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Benign	0.79
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs10497621; hg19: chr2-183997443;