2-127701554-A-G

Variant names:

• chr2-127701554-A-G
• rs777910385
• NM_032740.4:c.26A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032740.4(SFT2D3):​c.26A>G​(p.Gln9Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000247 in 1,212,858 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q9L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: SFT2D3 NM_032740.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.81
• Publications: 0 publications found

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]

ENSG00000293688 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFT2D3	NM_032740.4	c.26A>G	p.Gln9Arg	missense_variant	Exon 1 of 1	ENST00000310981.6	NP_116129.3
WDR33	NM_018383.5	c.*4769T>C		3_prime_UTR_variant	Exon 22 of 22	ENST00000322313.9	NP_060853.3
WDR33	XM_011511436.2	c.*4769T>C		3_prime_UTR_variant	Exon 22 of 22		XP_011509738.1
WDR33	XM_005263697.4	c.*4939T>C		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.26A>G	p.Gln9Arg	missense_variant	Exon 1 of 1	6	NM_032740.4	ENSP00000310803.3
WDR33	ENST00000322313.9	c.*4769T>C		3_prime_UTR_variant	Exon 22 of 22	1	NM_018383.5	ENSP00000325377.3
ENSG00000293688	ENST00000718293.1	n.-94T>C		upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000247 AC: 3 AN: 1212858 Hom.: 0 Cov.: 30 AF XY: 0.00000505 AC XY: 3 AN XY: 593694

African (AFR) AF: 0.0000408 AC: 1 AN: 24534

American (AMR) AF: 0.00 AC: 0 AN: 12756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17638

East Asian (EAS) AF: 0.00 AC: 0 AN: 28426

South Asian (SAS) AF: 0.00 AC: 0 AN: 51920

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35902

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3288

European-Non Finnish (NFE) AF: 0.00000202 AC: 2 AN: 990016

Other (OTH) AF: 0.00 AC: 0 AN: 48378

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0082	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.67	T
M_CAP	Pathogenic	0.92	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.8
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.098
Sift	Benign	0.079	T
Sift4G	Uncertain	0.032	D
Polyphen		1.0	D
Vest4		0.13
MutPred		0.20		Gain of MoRF binding (P = 0.0077);
MVP		0.89
ClinPred		0.95	D
GERP RS		3.9
PromoterAI		0.043	Neutral
Varity_R		0.36
gMVP		0.46
Mutation Taster		=64/36	polymorphism

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

Other links and lift over

dbSNP: rs777910385; hg19: chr2-128459128;