14-52029689-C-T

Position:

• chr14-52029689-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007361.4(NID2):​c.2259G>A​(p.Glu753Glu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.913 in 1,612,842 control chromosomes in the GnomAD database, including 673,920 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.87 (57938 hom., cov: 32)
  • Exomes 𝑓: 0.92 (615982 hom.)
• Consequence: NID2 NM_007361.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.00003978
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.41

Genes affected

NID2 (HGNC:13389): (nidogen 2) This gene encodes a member of the nidogen family of basement membrane proteins. This protein is a cell-adhesion protein that binds collagens I and IV and laminin and may be involved in maintaining the structure of the basement membrane.[provided by RefSeq, Jun 2010]

NID2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NID2	NM_007361.4	c.2259G>A	p.Glu753Glu	splice_region_variant, synonymous_variant	10/22	ENST00000216286.10	NP_031387.3
NID2	XM_005267405.5	c.2340G>A	p.Glu780Glu	splice_region_variant, synonymous_variant	9/21		XP_005267462.1
NID2	XM_005267406.5	c.2340G>A	p.Glu780Glu	splice_region_variant, synonymous_variant	9/20		XP_005267463.1
NID2	XM_005267407.5	c.2259G>A	p.Glu753Glu	splice_region_variant, synonymous_variant	10/21		XP_005267464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NID2	ENST00000216286.10	c.2259G>A	p.Glu753Glu	splice_region_variant, synonymous_variant	10/22	1	NM_007361.4	ENSP00000216286.4
NID2	ENST00000556572.1	c.207G>A	p.Glu69Glu	splice_region_variant, synonymous_variant	2/13	2		ENSP00000452190.1
NID2	ENST00000554284.1	n.441G>A		splice_region_variant, non_coding_transcript_exon_variant	4/5	5

Frequencies

GnomAD3 genomes AF: 0.869 AC: 132177 AN: 152094 Hom.: 57918 Cov.: 32

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.914

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.919

Gnomad OTH AF: 0.866

GnomAD3 exomes AF: 0.911 AC: 228575 AN: 251022 Hom.: 104487 AF XY: 0.912 AC XY: 123723 AN XY: 135644

Gnomad AFR exome AF: 0.744

Gnomad AMR exome AF: 0.936

Gnomad ASJ exome AF: 0.816

Gnomad EAS exome AF: 0.976

Gnomad SAS exome AF: 0.932

Gnomad FIN exome AF: 0.921

Gnomad NFE exome AF: 0.918

Gnomad OTH exome AF: 0.892

GnomAD4 exome AF: 0.918 AC: 1340244 AN: 1460630 Hom.: 615982 Cov.: 38 AF XY: 0.917 AC XY: 666665 AN XY: 726620

Gnomad4 AFR exome AF: 0.739

Gnomad4 AMR exome AF: 0.931

Gnomad4 ASJ exome AF: 0.822

Gnomad4 EAS exome AF: 0.964

Gnomad4 SAS exome AF: 0.932

Gnomad4 FIN exome AF: 0.921

Gnomad4 NFE exome AF: 0.923

Gnomad4 OTH exome AF: 0.898

GnomAD4 genome AF: 0.869 AC: 132250 AN: 152212 Hom.: 57938 Cov.: 32 AF XY: 0.869 AC XY: 64658 AN XY: 74408

Gnomad4 AFR AF: 0.749

Gnomad4 AMR AF: 0.892

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.968

Gnomad4 SAS AF: 0.933

Gnomad4 FIN AF: 0.914

Gnomad4 NFE AF: 0.919

Gnomad4 OTH AF: 0.868

Alfa AF: 0.905 Hom.: 133886

Bravo AF: 0.862

Asia WGS AF: 0.941 AC: 3274 AN: 3478

EpiCase AF: 0.900

EpiControl AF: 0.900

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.69
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000040
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.26		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2273431; hg19: chr14-52496407;