chr2-127701872-G-A

Variant names:

• chr2-127701872-G-A
• NM_032740.4:c.344G>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_032740.4(SFT2D3):​c.344G>A​(p.Gly115Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000764 in 1,308,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: SFT2D3 NM_032740.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.46

Genes affected

SFT2D3 (HGNC:28767): (SFT2 domain containing 3) Predicted to be involved in protein transport and vesicle-mediated transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

WDR33 (HGNC:25651): (WD repeat domain 33) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene is highly expressed in testis and the protein is localized to the nucleus. This gene may play important roles in the mechanisms of cytodifferentiation and/or DNA recombination. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.987

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFT2D3	NM_032740.4	c.344G>A	p.Gly115Asp	missense_variant	Exon 1 of 1	ENST00000310981.6	NP_116129.3
WDR33	NM_018383.5	c.*4451C>T		3_prime_UTR_variant	Exon 22 of 22	ENST00000322313.9	NP_060853.3
WDR33	XM_011511436.2	c.*4451C>T		3_prime_UTR_variant	Exon 22 of 22		XP_011509738.1
WDR33	XM_005263697.4	c.*4621C>T		3_prime_UTR_variant	Exon 21 of 21		XP_005263754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFT2D3	ENST00000310981.6	c.344G>A	p.Gly115Asp	missense_variant	Exon 1 of 1	6	NM_032740.4	ENSP00000310803.3
WDR33	ENST00000322313	c.*4451C>T		3_prime_UTR_variant	Exon 22 of 22	1	NM_018383.5	ENSP00000325377.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.64e-7 AC: 1 AN: 1308882 Hom.: 0 Cov.: 31 AF XY: 0.00000155 AC XY: 1 AN XY: 645930

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000366

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.78	T
M_CAP	Pathogenic	0.91	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Uncertain	0.43	D
MutationAssessor	Pathogenic	3.6	H
PrimateAI	Pathogenic	0.94	D
PROVEAN	Pathogenic	-6.8	D
REVEL	Pathogenic	0.85
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.81
MutPred		0.93		Loss of MoRF binding (P = 0.0422);
MVP		0.84
ClinPred		1.0	D
GERP RS		3.5
Varity_R		0.96
gMVP		0.87

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: chr2-128459446;