14-52011011-A-G

Position:

• chr14-52011011-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007361.4(NID2):​c.3587T>C​(p.Ile1196Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NID2 NM_007361.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.21

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 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=0.29901916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NID2	NM_007361.4	c.3587T>C	p.Ile1196Thr	missense_variant	18/22	ENST00000216286.10	NP_031387.3
NID2	XM_005267405.5	c.3668T>C	p.Ile1223Thr	missense_variant	17/21		XP_005267462.1
NID2	XM_005267406.5	c.3524T>C	p.Ile1175Thr	missense_variant	16/20		XP_005267463.1
NID2	XM_005267407.5	c.3443T>C	p.Ile1148Thr	missense_variant	17/21		XP_005267464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NID2	ENST00000216286.10	c.3587T>C	p.Ile1196Thr	missense_variant	18/22	1	NM_007361.4	ENSP00000216286.4
NID2	ENST00000556572.1	c.1391T>C	p.Ile464Thr	missense_variant	9/13	2		ENSP00000452190.1
NID2	ENST00000553297.1	n.505T>C		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2023

The c.3587T>C (p.I1196T) alteration is located in exon 18 (coding exon 18) of the NID2 gene. This alteration results from a T to C substitution at nucleotide position 3587, causing the isoleucine (I) at amino acid position 1196 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	0.20
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.28	T;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.49	N
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.3	N;.
REVEL	Benign	0.14
Sift	Benign	0.30	T;.
Sift4G	Benign	0.083	T;T
Polyphen		0.081	B;.
Vest4		0.42
MutPred		0.67		Gain of catalytic residue at L1191 (P = 0);.;
MVP		0.41
MPC		0.13
ClinPred		0.60	D
GERP RS		4.9
Varity_R		0.26
gMVP		0.55

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.

Other links and lift over

hg19: chr14-52477729; COSMIC: COSV53501483; COSMIC: COSV53501483;