2-185739377-G-A

Variant names:

• chr2-185739377-G-A
• NM_173651.4:c.131G>A

Variant summary

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

The NM_173651.4(FSIP2):​c.131G>A​(p.Gly44Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,008 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: FSIP2 NM_173651.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.77
• Publications: 0 publications found

Genes affected

FSIP2 (HGNC:21675): (fibrous sheath interacting protein 2) This gene encodes a protein associated with the sperm fibrous sheath. Genes encoding most of the fibrous-sheath associated proteins genes are transcribed only during the postmeiotic period of spermatogenesis. The protein encoded by this gene is specific to spermatogenic cells. Copy number variation in this gene may be associated with testicular germ cell tumors. Pseudogenes associated with this gene are reported on chromosomes 2 and X. [provided by RefSeq, Aug 2016]

FSIP2-AS1 (HGNC:40978): (FSIP2 antisense RNA 1)

FSIP2-AS2 (HGNC:54061): (FSIP2 antisense RNA 2)

ACMG classification

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173651.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSIP2	NM_173651.4	MANE Select	c.131G>A	p.Gly44Glu	missense	Exon 2 of 23	NP_775922.3	Q5CZC0-1
	FSIP2-AS2	NR_110217.1		n.99+1002C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSIP2	ENST00000424728.6	TSL:5 MANE Select	c.131G>A	p.Gly44Glu	missense	Exon 2 of 23	ENSP00000401306.1	Q5CZC0-1
	FSIP2	ENST00000465275.1	TSL:3	n.92G>A		non_coding_transcript_exon	Exon 1 of 2
	FSIP2-AS1	ENST00000427269.2	TSL:5	n.101+1002C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383008 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 682464

African (AFR) AF: 0.00 AC: 0 AN: 31418

American (AMR) AF: 0.00 AC: 0 AN: 35520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25116

East Asian (EAS) AF: 0.00 AC: 0 AN: 35620

South Asian (SAS) AF: 0.00 AC: 0 AN: 79054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34094

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5688

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078528

Other (OTH) AF: 0.00 AC: 0 AN: 57970

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.082	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.8
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.43
MVP		0.58
ClinPred		0.98	D
GERP RS		3.8
Varity_R		0.36
gMVP		0.40
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr2-186604104;