NM_144696.6:c.3032-1715G>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144696.6(AXDND1):​c.3032-1715G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000315 in 634,514 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: AXDND1 NM_144696.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXDND1	NM_144696.6	c.3032-1715G>A		intron_variant	Intron 25 of 25	ENST00000367618.8	NP_653297.3
NPHS2	NM_014625.4	c.795-116C>T		intron_variant	Intron 6 of 7	ENST00000367615.9	NP_055440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AXDND1	ENST00000367618.8	c.3032-1715G>A		intron_variant	Intron 25 of 25	1	NM_144696.6	ENSP00000356590.3
NPHS2	ENST00000367615.9	c.795-116C>T		intron_variant	Intron 6 of 7	1	NM_014625.4	ENSP00000356587.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000315 AC: 2 AN: 634514 Hom.: 0 AF XY: 0.00000590 AC XY: 2 AN XY: 338754

African (AFR) AF: 0.00 AC: 0 AN: 17696

American (AMR) AF: 0.00 AC: 0 AN: 34752

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20284

East Asian (EAS) AF: 0.00 AC: 0 AN: 32872

South Asian (SAS) AF: 0.00 AC: 0 AN: 63750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4194

European-Non Finnish (NFE) AF: 0.00000518 AC: 2 AN: 386174

Other (OTH) AF: 0.00 AC: 0 AN: 33158

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.48
PhyloP100		-0.33

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;