NM_001042424.3:c.32C>A

Variant names:

• chr4-1900686-C-A
• NM_001042424.3:c.32C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001042424.3(NSD2):​c.32C>A​(p.Ser11Tyr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NSD2 NM_001042424.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.72

Genes affected

NSD2 (HGNC:12766): (nuclear receptor binding SET domain protein 2) This gene encodes a protein that contains four domains present in other developmental proteins: a PWWP domain, an HMG box, a SET domain, and a PHD-type zinc finger. It is expressed ubiquitously in early development. Wolf-Hirschhorn syndrome (WHS) is a malformation syndrome associated with a hemizygous deletion of the distal short arm of chromosome 4. This gene maps to the 165 kb WHS critical region and has also been involved in the chromosomal translocation t(4;14)(p16.3;q32.3) in multiple myelomas. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. Some transcript variants are nonsense-mediated mRNA (NMD) decay candidates, hence not represented as reference sequences. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21266025).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NSD2	NM_001042424.3	c.32C>A	p.Ser11Tyr	missense_variant	Exon 2 of 22	ENST00000508803.6	NP_001035889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSD2	ENST00000508803.6	c.32C>A	p.Ser11Tyr	missense_variant	Exon 2 of 22	1	NM_001042424.3	ENSP00000423972.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.;.;.;T;T;.;T;.;T;.;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	.;T;.;T;.;T;T;.;.;T;T;T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.21	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.33	D
MutationAssessor	Benign	1.5	L;.;L;.;L;L;L;L;L;.;L;L
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.6	N;D;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.086	T;D;D;T;T;T;D;T;D;D;D;D
Sift4G	Benign	0.16	T;D;T;T;T;T;T;T;T;T;T;T
Polyphen		0.64	P;.;D;.;P;P;D;P;D;.;D;P
Vest4		0.32
MutPred		0.41		Loss of disorder (P = 0);Loss of disorder (P = 0);Loss of disorder (P = 0);Loss of disorder (P = 0);Loss of disorder (P = 0);Loss of disorder (P = 0);Loss of disorder (P = 0);Loss of disorder (P = 0);Loss of disorder (P = 0);Loss of disorder (P = 0);Loss of disorder (P = 0);Loss of disorder (P = 0);
MVP		0.39
MPC		0.59
ClinPred		0.59	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.041
gMVP		0.22

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: chr4-1902413;