chr14-74480021-TA-T

Position:

• chr14-74480021-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000555619.6(NPC2):​c.*252del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,373,998 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0040 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (3 hom.)
• Consequence: NPC2 ENST00000555619.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.320

Genes affected

NPC2 (HGNC:14537): (NPC intracellular cholesterol transporter 2) This gene encodes a protein containing a lipid recognition domain. The encoded protein may function in regulating the transport of cholesterol through the late endosomal/lysosomal system. Mutations in this gene have been associated with Niemann-Pick disease, type C2 and frontal lobe atrophy. [provided by RefSeq, Jul 2008]

SYNDIG1L (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 14-74480021-TA-T is Benign according to our data. Variant chr14-74480021-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1202055.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.004 (599/149804) while in subpopulation AFR AF= 0.0138 (563/40888). AF 95% confidence interval is 0.0128. There are 6 homozygotes in gnomad4. There are 275 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPC2	NM_006432.5	c.*252del		3_prime_UTR_variant	5/5	ENST00000555619.6	NP_006423.1
SYNDIG1L	XM_017021600.2	c.-5776del		5_prime_UTR_variant	1/4		XP_016877089.1
NPC2	NM_001363688.1	c.*596del		3_prime_UTR_variant	4/4		NP_001350617.1
NPC2	NM_001375440.1	c.*252del		3_prime_UTR_variant	4/4		NP_001362369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPC2	ENST00000555619.6	c.*252del		3_prime_UTR_variant	5/5	1	NM_006432.5	ENSP00000451112	P4

Frequencies

GnomAD3 genomes AF: 0.00399 AC: 597 AN: 149688 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00187

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000149

Gnomad OTH AF: 0.00293

GnomAD4 exome AF: 0.00107 AC: 1315 AN: 1224194 Hom.: 3 Cov.: 31 AF XY: 0.00115 AC XY: 686 AN XY: 599086

Gnomad4 AFR exome AF: 0.0151

Gnomad4 AMR exome AF: 0.00272

Gnomad4 ASJ exome AF: 0.00141

Gnomad4 EAS exome AF: 0.00229

Gnomad4 SAS exome AF: 0.000936

Gnomad4 FIN exome AF: 0.00230

Gnomad4 NFE exome AF: 0.000530

Gnomad4 OTH exome AF: 0.00210

GnomAD4 genome AF: 0.00400 AC: 599 AN: 149804 Hom.: 6 Cov.: 32 AF XY: 0.00376 AC XY: 275 AN XY: 73048

Gnomad4 AFR AF: 0.0138

Gnomad4 AMR AF: 0.00187

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000196

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000149

Gnomad4 OTH AF: 0.00290

Alfa AF: 0.0000720 Hom.: 0

Bravo AF: 0.00425

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs369932535; hg19: chr14-74946724;