14-52010935-C-G

Position:

• chr14-52010935-C-G

Variant summary

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

The NM_007361.4(NID2):​c.3663G>C​(p.Lys1221Asn) 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. 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: -0.573

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=0.4033059).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NID2	NM_007361.4	c.3663G>C	p.Lys1221Asn	missense_variant	18/22	ENST00000216286.10	NP_031387.3
NID2	XM_005267405.5	c.3744G>C	p.Lys1248Asn	missense_variant	17/21		XP_005267462.1
NID2	XM_005267406.5	c.3600G>C	p.Lys1200Asn	missense_variant	16/20		XP_005267463.1
NID2	XM_005267407.5	c.3519G>C	p.Lys1173Asn	missense_variant	17/21		XP_005267464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NID2	ENST00000216286.10	c.3663G>C	p.Lys1221Asn	missense_variant	18/22	1	NM_007361.4	ENSP00000216286.4
NID2	ENST00000556572.1	c.1467G>C	p.Lys489Asn	missense_variant	9/13	2		ENSP00000452190.1
NID2	ENST00000553297.1	n.581G>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

Jul 19, 2022

The c.3663G>C (p.K1221N) alteration is located in exon 18 (coding exon 18) of the NID2 gene. This alteration results from a G to C substitution at nucleotide position 3663, causing the lysine (K) at amino acid position 1221 to be replaced by an asparagine (N). 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	0.38
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.18	N
LIST_S2	Uncertain	0.90	D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.40	T;T
MetaSVM	Uncertain	0.55	D
MutationAssessor	Uncertain	2.9	M;.
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.4	N;.
REVEL	Uncertain	0.41
Sift	Uncertain	0.017	D;.
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.35	B;.
Vest4		0.39
MutPred		0.66		Gain of catalytic residue at K1221 (P = 0.0121);.;
MVP		0.85
MPC		0.21
ClinPred		0.91	D
GERP RS		0.70
Varity_R		0.42
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr14-52477653;