2-38881536-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001145450.3(MORN2):c.311T>C(p.Phe104Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000173 in 1,388,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: MORN2 NM_001145450.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.82

Genes affected

MORN2 (HGNC:30166): (MORN repeat containing 2) Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be located in acrosomal vesicle and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.921

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MORN2	NM_001145450.3	c.311T>C	p.Phe104Ser	missense_variant	4/5	ENST00000644631.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MORN2	ENST00000644631.4	c.311T>C	p.Phe104Ser	missense_variant	4/5		NM_001145450.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000686 AC: 1 AN: 145782 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 76424

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000173

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000173 AC: 24 AN: 1388292 Hom.: 0 Cov.: 29 AF XY: 0.0000117 AC XY: 8 AN XY: 684168

Gnomad4 AFR exome AF: 0.0000324

Gnomad4 AMR exome AF: 0.00

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: 0.0000205

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000395 AC: 1

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

Jan 08, 2024

The c.95T>C (p.F32S) alteration is located in exon 4 (coding exon 1) of the MORN2 gene. This alteration results from a T to C substitution at nucleotide position 95, causing the phenylalanine (F) at amino acid position 32 to be replaced by a serine (S). 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	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.081	T;T;T;.;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D;.;.;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.92	D;D;D;D;D
MetaSVM	Benign	-0.37	T
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-5.4	D;D;D;.;D
REVEL	Uncertain	0.61
Sift	Uncertain	0.0030	D;D;D;.;D
Sift4G	Benign	0.26	T;T;T;.;D
Polyphen		0.95	P;P;P;.;.
Vest4		0.76
MutPred		0.81		Gain of disorder (P = 0.0037);Gain of disorder (P = 0.0037);Gain of disorder (P = 0.0037);.;.;
MVP		0.52
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.84
gMVP		0.77

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

LitVar

Other links and lift over

dbSNP: rs749052669; hg19: chr2-39108677;