Variant 14-52010952-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_007361.4(NID2):c.3646G>T(p.Asp1216Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NID2
NM_007361.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.84

Variant links:

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 links:

NID2 (HGNC:):

NID2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.914

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NID2	NM_007361.4 linkuse as main transcript	c.3646G>T	p.Asp1216Tyr	missense_variant	18/22	ENST00000216286.10	NP_031387.3	Q14112-1
NID2	XM_005267405.5 linkuse as main transcript	c.3727G>T	p.Asp1243Tyr	missense_variant	17/21		XP_005267462.1
NID2	XM_005267406.5 linkuse as main transcript	c.3583G>T	p.Asp1195Tyr	missense_variant	16/20		XP_005267463.1
NID2	XM_005267407.5 linkuse as main transcript	c.3502G>T	p.Asp1168Tyr	missense_variant	17/21		XP_005267464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NID2	ENST00000216286.10 linkuse as main transcript	c.3646G>T	p.Asp1216Tyr	missense_variant	18/22	1	NM_007361.4	ENSP00000216286.4	Q14112-1
NID2	ENST00000556572.1 linkuse as main transcript	c.1450G>T	p.Asp484Tyr	missense_variant	9/13	2		ENSP00000452190.1	H0YJV3
NID2	ENST00000553297.1 linkuse as main transcript	n.564G>T		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 30, 2022

The c.3646G>T (p.D1216Y) alteration is located in exon 18 (coding exon 18) of the NID2 gene. This alteration results from a G to T substitution at nucleotide position 3646, causing the aspartic acid (D) at amino acid position 1216 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Pathogenic

0.57

BayesDel_noAF

Pathogenic

0.58

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.74

D;T

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

D;D

M_CAP

Uncertain

0.25

MetaRNN

Pathogenic

0.91

D;D

MetaSVM

Uncertain

0.67

MutationAssessor

Pathogenic

3.9

H;.

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-8.1

D;.

REVEL

Pathogenic

0.91

Sift

Uncertain

0.0010

D;.

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;.

Vest4

0.89

MutPred

0.65

Gain of catalytic residue at L1215 (P = 0.0313);.;

MVP

0.87

MPC

0.53

ClinPred

1.0

GERP RS

6.0

Varity_R

0.97

gMVP

0.96

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over