1-179552797-G-T

Variant names:

• chr1-179552797-G-T
• rs2274626
• NM_144696.6:c.3032-1715G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_144696.6(AXDND1):​c.3032-1715G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 785,896 control chromosomes in the GnomAD database, including 58,824 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (13881 hom., cov: 33)
  • Exomes 𝑓: 0.37 (44943 hom.)
• Consequence: AXDND1 NM_144696.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.331
• Publications: 15 publications found

Genes affected

AXDND1 (HGNC:26564): (axonemal dynein light chain domain containing 1)

NPHS2 (HGNC:13394): (NPHS2 stomatin family member, podocin) This gene encodes a protein that plays a role in the regulation of glomerular permeability. Mutations in this gene cause steroid-resistant nephrotic syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

NPHS2 Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 2

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Myriad Women’s Health, Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina, G2P
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-179552797-G-T is Benign according to our data. Variant chr1-179552797-G-T is described in ClinVar as Benign. ClinVar VariationId is 1289362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144696.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXDND1	NM_144696.6	MANE Select	c.3032-1715G>T		intron	N/A	NP_653297.3
	NPHS2	NM_014625.4	MANE Select	c.795-116C>A		intron	N/A	NP_055440.1
	NPHS2	NM_001297575.2		c.591-116C>A		intron	N/A	NP_001284504.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXDND1	ENST00000367618.8	TSL:1 MANE Select	c.3032-1715G>T		intron	N/A	ENSP00000356590.3
	NPHS2	ENST00000367615.9	TSL:1 MANE Select	c.795-116C>A		intron	N/A	ENSP00000356587.4
	AXDND1	ENST00000434088.1	TSL:1	c.2612-1715G>T		intron	N/A	ENSP00000391716.1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63300 AN: 151974 Hom.: 13856 Cov.: 33

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.405

GnomAD4 exome AF: 0.373 AC: 236209 AN: 633804 Hom.: 44943 AF XY: 0.372 AC XY: 125923 AN XY: 338374

African (AFR) AF: 0.556 AC: 9825 AN: 17668

American (AMR) AF: 0.428 AC: 14872 AN: 34740

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 6300 AN: 20274

East Asian (EAS) AF: 0.446 AC: 14652 AN: 32846

South Asian (SAS) AF: 0.395 AC: 25181 AN: 63732

European-Finnish (FIN) AF: 0.313 AC: 13000 AN: 41578

Middle Eastern (MID) AF: 0.423 AC: 1773 AN: 4188

European-Non Finnish (NFE) AF: 0.357 AC: 137867 AN: 385660

Other (OTH) AF: 0.385 AC: 12739 AN: 33118

GnomAD4 genome AF: 0.417 AC: 63373 AN: 152092 Hom.: 13881 Cov.: 33 AF XY: 0.414 AC XY: 30794 AN XY: 74364

African (AFR) AF: 0.553 AC: 22921 AN: 41474

American (AMR) AF: 0.436 AC: 6673 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1031 AN: 3468

East Asian (EAS) AF: 0.432 AC: 2231 AN: 5164

South Asian (SAS) AF: 0.397 AC: 1912 AN: 4820

European-Finnish (FIN) AF: 0.311 AC: 3291 AN: 10576

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23939 AN: 67984

Other (OTH) AF: 0.408 AC: 862 AN: 2114

Alfa AF: 0.368 Hom.: 17691

Bravo AF: 0.434

Asia WGS AF: 0.459 AC: 1598 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.91
DANN	Benign	0.50
PhyloP100		-0.33
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: rs2274626; hg19: chr1-179521932;