Variant 14-52010898-T-C 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.3700A>G(p.Ile1234Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

NID2
NM_007361.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.96

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, 0.841

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NID2	NM_007361.4 linkuse as main transcript	c.3700A>G	p.Ile1234Val	missense_variant	18/22	ENST00000216286.10	NP_031387.3	Q14112-1
NID2	XM_005267405.5 linkuse as main transcript	c.3781A>G	p.Ile1261Val	missense_variant	17/21		XP_005267462.1
NID2	XM_005267406.5 linkuse as main transcript	c.3637A>G	p.Ile1213Val	missense_variant	16/20		XP_005267463.1
NID2	XM_005267407.5 linkuse as main transcript	c.3556A>G	p.Ile1186Val	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.3700A>G	p.Ile1234Val	missense_variant	18/22	1	NM_007361.4	ENSP00000216286.4	Q14112-1
NID2	ENST00000556572.1 linkuse as main transcript	c.1504A>G	p.Ile502Val	missense_variant	9/13	2		ENSP00000452190.1	H0YJV3
NID2	ENST00000553297.1 linkuse as main transcript	n.618A>G		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251310

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000756

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

Jul 31, 2024

The c.3700A>G (p.I1234V) alteration is located in exon 18 (coding exon 18) of the NID2 gene. This alteration results from a A to G substitution at nucleotide position 3700, causing the isoleucine (I) at amino acid position 1234 to be replaced by a valine (V). 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

Benign

0.14

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

0.13

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.38

T;T

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.062

MetaRNN

Pathogenic

0.84

D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Uncertain

2.4

M;.

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-0.87

N;.

REVEL

Pathogenic

0.74

Sift

Uncertain

0.017

D;.

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.99

D;.

Vest4

0.75

MutPred

0.73

Gain of catalytic residue at D1237 (P = 0.0032);.;

MVP

0.94

MPC

0.44

ClinPred

0.70

GERP RS

6.0

Varity_R

0.29

gMVP

0.79

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over