Variant 14-52011599-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_007361.4(NID2):c.3505G>A(p.Ala1169Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,614,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

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: 4.13

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29560545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NID2	NM_007361.4 linkuse as main transcript	c.3505G>A	p.Ala1169Thr	missense_variant	17/22	ENST00000216286.10	NP_031387.3	Q14112-1
NID2	XM_005267405.5 linkuse as main transcript	c.3586G>A	p.Ala1196Thr	missense_variant	16/21		XP_005267462.1
NID2	XM_005267406.5 linkuse as main transcript	c.3442G>A	p.Ala1148Thr	missense_variant	15/20		XP_005267463.1
NID2	XM_005267407.5 linkuse as main transcript	c.3361G>A	p.Ala1121Thr	missense_variant	16/21		XP_005267464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NID2	ENST00000216286.10 linkuse as main transcript	c.3505G>A	p.Ala1169Thr	missense_variant	17/22	1	NM_007361.4	ENSP00000216286.4	Q14112-1
NID2	ENST00000556572.1 linkuse as main transcript	c.1309G>A	p.Ala437Thr	missense_variant	8/13	2		ENSP00000452190.1	H0YJV3
NID2	ENST00000553297.1 linkuse as main transcript	n.423G>A		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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

May 23, 2023

The c.3505G>A (p.A1169T) alteration is located in exon 17 (coding exon 17) of the NID2 gene. This alteration results from a G to A substitution at nucleotide position 3505, causing the alanine (A) at amino acid position 1169 to be replaced by a threonine (T). 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

0.12

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

T;T

Eigen

Benign

0.054

Eigen_PC

Benign

-0.013

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.4

D;.

REVEL

Benign

0.13

Sift

Benign

0.060

T;.

Sift4G

Uncertain

0.042

D;D

Polyphen

0.078

B;.

Vest4

0.24

MutPred

0.53

Gain of catalytic residue at L1171 (P = 0);.;

MVP

0.43

MPC

0.091

ClinPred

0.90

GERP RS

4.1

Varity_R

0.21

gMVP

0.77

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