chr14-52029689-C-A

Variant names:

• chr14-52029689-C-A
• rs2273431
• NM_007361.4:c.2259G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007361.4(NID2):​c.2259G>T​(p.Glu753Asp) variant causes a missense, splice region 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. 19/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NID2 NM_007361.4 missense, splice_region
• Scores: Splicing: ADA: 0.00001059
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.41
• Publications: 23 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06734428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NID2	NM_007361.4	c.2259G>T	p.Glu753Asp	missense_variant, splice_region_variant	Exon 10 of 22	ENST00000216286.10	NP_031387.3
NID2	XM_005267405.5	c.2340G>T	p.Glu780Asp	missense_variant, splice_region_variant	Exon 9 of 21		XP_005267462.1
NID2	XM_005267406.5	c.2340G>T	p.Glu780Asp	missense_variant, splice_region_variant	Exon 9 of 20		XP_005267463.1
NID2	XM_005267407.5	c.2259G>T	p.Glu753Asp	missense_variant, splice_region_variant	Exon 10 of 21		XP_005267464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NID2	ENST00000216286.10	c.2259G>T	p.Glu753Asp	missense_variant, splice_region_variant	Exon 10 of 22	1	NM_007361.4	ENSP00000216286.4
NID2	ENST00000556572.1	c.207G>T	p.Glu69Asp	missense_variant, splice_region_variant	Exon 2 of 13	2		ENSP00000452190.1
NID2	ENST00000554284.1	n.441G>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 4 of 5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461122 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 726844

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111422

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	0.0036	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	0.0080
DANN	Benign	0.32
DEOGEN2	Benign	0.043	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.067	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.16	N;.
PhyloP100		-3.4
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.56	N;.
REVEL	Benign	0.16
Sift	Benign	0.54	T;.
Sift4G	Benign	0.63	T;T
Polyphen		0.0	B;.
Vest4		0.084
MutPred		0.38		Gain of catalytic residue at P757 (P = 0.0059);.;
MVP		0.66
MPC		0.081
ClinPred		0.060	T
GERP RS		-7.1
Varity_R		0.044
gMVP		0.24
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000011
dbscSNV1_RF	Benign	0.0
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

Other links and lift over

dbSNP: rs2273431; hg19: chr14-52496407;