14-52006562-G-A

Position:

• chr14-52006562-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2 BP4_Strong BP6_Very_Strong

The NM_007361.4(NID2):​c.3979C>T​(p.His1327Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000288 in 1,613,754 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (1 hom.)
• Consequence: NID2 NM_007361.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.33

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]

RTRAF (HGNC:23169): (RNA transcription, translation and transport factor) Enables RNA binding activity; RNA polymerase II complex binding activity; and identical protein binding activity. Involved in negative regulation of protein kinase activity; positive regulation of transcription by RNA polymerase II; and tRNA splicing, via endonucleolytic cleavage and ligation. Located in microtubule cytoskeleton; nucleoplasm; and perinuclear region of cytoplasm. Part of tRNA-splicing ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

NID2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.010901511).
• BP6: Variant 14-52006562-G-A is Benign according to our data. Variant chr14-52006562-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 724770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NID2	NM_007361.4	c.3979C>T	p.His1327Tyr	missense_variant	20/22	ENST00000216286.10	NP_031387.3
RTRAF	NM_016039.3	c.*2046G>A		3_prime_UTR_variant	8/8	ENST00000261700.8	NP_057123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NID2	ENST00000216286.10	c.3979C>T	p.His1327Tyr	missense_variant	20/22	1	NM_007361.4	ENSP00000216286.4
RTRAF	ENST00000261700.8	c.*2046G>A		3_prime_UTR_variant	8/8	1	NM_016039.3	ENSP00000261700.3

Frequencies

GnomAD3 genomes AF: 0.00155 AC: 236 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000370 AC: 93 AN: 251416 Hom.: 0 AF XY: 0.000294 AC XY: 40 AN XY: 135880

Gnomad AFR exome AF: 0.00486

Gnomad AMR exome AF: 0.000231

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: 0.0000352

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000156 AC: 228 AN: 1461482 Hom.: 1 Cov.: 31 AF XY: 0.000128 AC XY: 93 AN XY: 727048

Gnomad4 AFR exome AF: 0.00532

Gnomad4 AMR exome AF: 0.000179

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: 0.0000189

Gnomad4 OTH exome AF: 0.000282

GnomAD4 genome AF: 0.00155 AC: 236 AN: 152272 Hom.: 0 Cov.: 32 AF XY: 0.00167 AC XY: 124 AN XY: 74444

Gnomad4 AFR AF: 0.00529

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000312 Hom.: 0

Bravo AF: 0.00174

ESP6500AA AF: 0.00499 AC: 22

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000436 AC: 53

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.011	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.91	L;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.5	D;.
REVEL	Benign	0.16
Sift	Benign	0.14	T;.
Sift4G	Benign	0.10	T;T
Polyphen		0.019	B;.
Vest4		0.56
MVP		0.39
MPC		0.11
ClinPred		0.045	T
GERP RS		6.0
Varity_R		0.30
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs139599501; hg19: chr14-52473280;